Variant 7-156676637-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030936.4(RNF32):c.1071G>T(p.Lys357Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,172 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RNF32
NM_030936.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF32	NM_030936.4 linkuse as main transcript	c.1071G>T	p.Lys357Asn	missense_variant	9/9	ENST00000317955.10	NP_112198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF32	ENST00000317955.10 linkuse as main transcript	c.1071G>T	p.Lys357Asn	missense_variant	9/9	1	NM_030936.4	ENSP00000315950	P1	Q9H0A6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251318

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135816

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461172

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 14, 2022

The c.1071G>T (p.K357N) alteration is located in exon 9 (coding exon 8) of the RNF32 gene. This alteration results from a G to T substitution at nucleotide position 1071, causing the lysine (K) at amino acid position 357 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.75

.;.;.;T

M_CAP

Uncertain

0.087

MetaRNN

Uncertain

0.54

D;D;D;D

MetaSVM

Uncertain

0.015

MutationAssessor

Pathogenic

3.1

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.3

D;D;D;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.42

MutPred

0.66

Loss of methylation at K357 (P = 0.0025);Loss of methylation at K357 (P = 0.0025);Loss of methylation at K357 (P = 0.0025);Loss of methylation at K357 (P = 0.0025);

MVP

0.89

MPC

0.71

ClinPred

0.98

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over