Genetic Variant TMEM232:p.Leu650His (chr5-110420605-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001039763.4(TMEM232):c.1949T>A(p.Leu650His) variant causes a missense change. The variant allele was found at a frequency of 0.0000257 in 1,481,016 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

TMEM232
NM_001039763.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.1949T>A	p.Leu650His	missense	Exon 14 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.1949T>A	p.Leu650His	missense	Exon 14 of 14	ENSP00000401477.2	C9JQI7-1
TMEM232	ENST00000512003.7	TSL:1	n.*1243T>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000427785.2	E5RG73
TMEM232	ENST00000515518.6	TSL:1	n.1621T>A		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152066

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1328950

Hom.:

Cov.:

AF XY:

0.0000214

AC XY:

AN XY:

654804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27274

American (AMR)

AF:

0.00

AC:

AN:

20726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23442

East Asian (EAS)

AF:

0.00

AC:

AN:

32826

South Asian (SAS)

AF:

0.00

AC:

AN:

68372

European-Finnish (FIN)

AF:

0.0000299

AC:

AN:

33430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5464

European-Non Finnish (NFE)

AF:

0.0000273

AC:

AN:

1061936

Other (OTH)

AF:

0.00

AC:

AN:

55480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.0000526

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67982

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ClinVar

ClinVar submissions as Germline

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

Uncertain

0.52

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.40

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.81

PhyloP100

4.1

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.28

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.67

MVP

0.21

ClinPred

0.92

GERP RS

4.4

Varity_R

0.25

gMVP

0.083

Mutation Taster

=67/33

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

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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