Genetic Variant NM_001039763.4:c.982G>A (chr5-110606208-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001039763.4(TMEM232):c.982G>A(p.Val328Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,548,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V328L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

TMEM232
NM_001039763.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.440

Publications

2 publications found

Variant links:

Genes affected

TMEM232 (HGNC:37270): (transmembrane protein 232) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM232 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012728184).

BP6

Variant 5-110606208-C-T is Benign according to our data. Variant chr5-110606208-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3179221.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039763.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM232	NM_001039763.4	MANE Select	c.982G>A	p.Val328Ile	missense	Exon 9 of 14	NP_001034852.3	C9JQI7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM232	ENST00000455884.7	TSL:2 MANE Select	c.982G>A	p.Val328Ile	missense	Exon 9 of 14	ENSP00000401477.2	C9JQI7-1
TMEM232	ENST00000512003.7	TSL:1	n.*524G>A		non_coding_transcript_exon	Exon 7 of 11	ENSP00000427785.2	E5RG73
TMEM232	ENST00000515518.6	TSL:1	n.902G>A		non_coding_transcript_exon	Exon 8 of 13

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000766

AC:

AN:

156628

AF XY:

0.0000844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000459

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000415

AC:

AN:

1396322

Hom.:

Cov.:

AF XY:

0.0000421

AC XY:

AN XY:

688706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31554

American (AMR)

AF:

0.00

AC:

AN:

35680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25084

East Asian (EAS)

AF:

0.000477

AC:

AN:

35668

South Asian (SAS)

AF:

0.000190

AC:

AN:

78818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.0000195

AC:

AN:

1076890

Other (OTH)

AF:

0.0000865

AC:

AN:

57820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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:

0.0000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000329

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000811

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.058

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.3

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0017

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.40

M_CAP

Benign

0.0045

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

PhyloP100

-0.44

PrimateAI

Benign

0.31

PROVEAN

Benign

0.61

REVEL

Benign

0.012

Sift

Benign

0.30

Sift4G

Benign

0.29

Polyphen

0.0020

Vest4

0.047

MVP

0.014

ClinPred

0.020

GERP RS

-6.7

Varity_R

0.035

gMVP

0.025

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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