Variant 5-110424833-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001039763.4(TMEM232):c.1787T>C(p.Ile596Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00153 in 1,548,804 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 5 hom. )

Consequence

TMEM232
NM_001039763.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037774056).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM232	NM_001039763.4 linkuse as main transcript	c.1787T>C	p.Ile596Thr	missense_variant	13/14	ENST00000455884.7	NP_001034852.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM232	ENST00000455884.7 linkuse as main transcript	c.1787T>C	p.Ile596Thr	missense_variant	13/14	2	NM_001039763.4	ENSP00000401477	P1	C9JQI7-1

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000949

AC:

144

AN:

151760

Hom.:

AF XY:

0.000932

AC XY:

AN XY:

80470

show subpopulations

Gnomad AFR exome

AF:

0.000255

Gnomad AMR exome

AF:

0.000124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000180

Gnomad FIN exome

AF:

0.000591

Gnomad NFE exome

AF:

0.00209

Gnomad OTH exome

AF:

0.000701

GnomAD4 exome

AF:

0.00159

AC:

2214

AN:

1396532

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1094

AN XY:

688742

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.0000847

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000127

Gnomad4 FIN exome

AF:

0.000772

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.00104

AC:

158

AN:

152272

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00199

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00158

Hom.:

Bravo

AF:

0.000918

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00283

AC:

ExAC

AF:

0.000833

AC:

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

Aug 10, 2021

The c.1787T>C (p.I596T) alteration is located in exon 13 (coding exon 12) of the TMEM232 gene. This alteration results from a T to C substitution at nucleotide position 1787, causing the isoleucine (I) at amino acid position 596 to be replaced by a threonine (T). 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

Benign

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.54

M_CAP

Benign

0.020

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.094

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0060

Polyphen

0.73

Vest4

0.66

MVP

0.067

ClinPred

0.050

GERP RS

4.7

Varity_R

0.17

gMVP

0.057

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