Genetic Variant TMEM37:p.Gln69Lys (chr2-119437072-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_183240.3(TMEM37):c.205C>A(p.Gln69Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,084,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TMEM37
NM_183240.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

Publications

0 publications found

Variant links:

Genes affected

TMEM37 (HGNC:18216): (transmembrane protein 37) Predicted to enable calcium channel activity and voltage-gated ion channel activity. Predicted to be involved in calcium ion transmembrane transport and regulation of ion transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM37 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10662061).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183240.3. 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
	TMEM37	NM_183240.3	MANE Select	c.205C>A	p.Gln69Lys	missense	Exon 2 of 2	NP_899063.2	Q8WXS4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM37	ENST00000306406.5	TSL:1 MANE Select	c.205C>A	p.Gln69Lys	missense	Exon 2 of 2	ENSP00000303148.4	Q8WXS4
TMEM37	ENST00000911072.1		c.271C>A	p.Gln91Lys	missense	Exon 3 of 3	ENSP00000581131.1
TMEM37	ENST00000409826.1	TSL:3	c.241C>A	p.Gln81Lys	missense	Exon 2 of 2	ENSP00000387015.1	E7EMC0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000180

AC:

AN:

55672

AF XY:

0.0000342

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000430

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000148

AC:

AN:

1084126

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

540874

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22204

American (AMR)

AF:

0.00

AC:

AN:

28100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18004

East Asian (EAS)

AF:

0.00

AC:

AN:

32214

South Asian (SAS)

AF:

0.00

AC:

AN:

60110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4606

European-Non Finnish (NFE)

AF:

0.0000193

AC:

AN:

830066

Other (OTH)

AF:

0.00

AC:

AN:

45432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ExAC

AF:

0.00000825

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

0.089

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.20

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.38

M_CAP

Benign

0.0025

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

1.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

REVEL

Benign

0.083

Sift

Benign

0.52

Sift4G

Benign

0.68

Polyphen

0.018

Vest4

0.12

MVP

0.26

MPC

0.46

ClinPred

0.95

GERP RS

3.6

Varity_R

0.089

gMVP

0.12

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over