Genetic Variant NM_001039763.4:c.1787T>C (chr5-110424833-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 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: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

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.1787T>C	p.Ile596Thr	missense	Exon 13 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.1787T>C	p.Ile596Thr	missense	Exon 13 of 14	ENSP00000401477.2	C9JQI7-1
TMEM232	ENST00000512003.7	TSL:1	n.*1081T>C		non_coding_transcript_exon	Exon 10 of 11	ENSP00000427785.2	E5RG73
TMEM232	ENST00000515518.6	TSL:1	n.1459T>C		non_coding_transcript_exon	Exon 11 of 13

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

GnomAD2 exomes

AF:

0.000949

AC:

144

AN:

151760

AF XY:

0.000932

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 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

African (AFR)

AF:

0.000127

AC:

AN:

31476

American (AMR)

AF:

0.0000847

AC:

AN:

35418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25084

East Asian (EAS)

AF:

0.00

AC:

AN:

35586

South Asian (SAS)

AF:

0.000127

AC:

AN:

78656

European-Finnish (FIN)

AF:

0.000772

AC:

AN:

49234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00195

AC:

2098

AN:

1077496

Other (OTH)

AF:

0.00105

AC:

AN:

57896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

102

205

307

410

512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.00104

AC:

158

AN:

152272

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41568

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00199

AC:

135

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.00158

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

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

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

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

PhyloP100

4.8

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

Mutation Taster

=90/10

polymorphism

(source)

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

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