7-156675715-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_030936.4(RNF32):c.704G>A(p.Arg235His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000736 in 1,359,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

RNF32
NM_030936.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44

Publications

2 publications found

Variant links:

Genes affected

RNF32 (HGNC:17118): (ring finger protein 32) The protein encoded by this gene contains two RING ring finger motifs. RING finger motifs are present in a variety of functionally distinct proteins and are known to be involved in protein-DNA or protein-protein interactions. This gene was found to be expressed during spermatogenesis, most likely in spermatocytes and/or in spermatids. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

RNF32 links:

LMBR1 (HGNC:13243): (limb development membrane protein 1) This gene encodes a member of the LMBR1-like membrane protein family. Another member of this protein family has been shown to be a lipocalin transmembrane receptor. A highly conserved, cis-acting regulatory module for the sonic hedgehog gene is located within an intron of this gene. Consequently, disruption of this genic region can alter sonic hedgehog expression and affect limb patterning, but it is not known if this gene functions directly in limb development. Mutations and chromosomal deletions and rearrangements in this genic region are associated with acheiropody and preaxial polydactyly, which likely result from altered sonic hedgehog expression. [provided by RefSeq, Jul 2008]

LMBR1 Gene-Disease associations (from GenCC):

polydactyly of a triphalangeal thumb
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
acheiropody
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
hypoplastic tibiae-postaxial polydactyly syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
laurin-Sandrow syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
syndactyly type 4
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
triphalangeal thumb-polysyndactyly syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LMBR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.366139).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030936.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF32	NM_030936.4	MANE Select	c.704G>A	p.Arg235His	missense	Exon 8 of 9	NP_112198.1	Q9H0A6-1
RNF32	NM_001184996.2		c.704G>A	p.Arg235His	missense	Exon 8 of 9	NP_001171925.1	Q9H0A6-1
RNF32	NM_001184997.1		c.704G>A	p.Arg235His	missense	Exon 8 of 9	NP_001171926.1	Q9H0A6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF32	ENST00000317955.10	TSL:1 MANE Select	c.704G>A	p.Arg235His	missense	Exon 8 of 9	ENSP00000315950.5	Q9H0A6-1
RNF32	ENST00000392743.6	TSL:1	c.704G>A	p.Arg235His	missense	Exon 8 of 9	ENSP00000376499.2	Q9H0A6-1
RNF32	ENST00000432459.6	TSL:1	c.704G>A	p.Arg235His	missense	Exon 8 of 9	ENSP00000405588.2	Q9H0A6-1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

149944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000298

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251378

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000661

AC:

AN:

1209604

Hom.:

Cov.:

AF XY:

0.00000659

AC XY:

AN XY:

607222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31472

American (AMR)

AF:

0.00

AC:

AN:

42906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21446

East Asian (EAS)

AF:

0.00

AC:

AN:

35886

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81366

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4836

European-Non Finnish (NFE)

AF:

0.00000782

AC:

AN:

895324

Other (OTH)

AF:

0.00

AC:

AN:

49972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000133

AC:

AN:

149944

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73162

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41300

American (AMR)

AF:

0.00

AC:

AN:

15136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

5036

South Asian (SAS)

AF:

0.00

AC:

AN:

4626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000298

AC:

AN:

67104

Other (OTH)

AF:

0.00

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

0.099

Eigen_PC

Benign

0.047

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.016

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

PhyloP100

3.4

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.21

Sift

Uncertain

0.013

Sift4G

Uncertain

0.031

Polyphen

0.85

Vest4

0.64

MVP

0.53

MPC

0.67

ClinPred

0.97

GERP RS

5.2

Varity_R

0.32

gMVP

0.40

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over