Variant 2-119437072-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 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

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:

TMEM37 (HGNC:):

TMEM37 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM37	NM_183240.3 linkuse as main transcript	c.205C>A	p.Gln69Lys	missense_variant	2/2	ENST00000306406.5	NP_899063.2	Q8WXS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM37	ENST00000306406.5 linkuse as main transcript	c.205C>A	p.Gln69Lys	missense_variant	2/2	1	NM_183240.3	ENSP00000303148.4	Q8WXS4
TMEM37	ENST00000409826.1 linkuse as main transcript	c.241C>A	p.Gln81Lys	missense_variant	2/2	3		ENSP00000387015.1	E7EMC0
TMEM37	ENST00000465296.1 linkuse as main transcript	n.345C>A		non_coding_transcript_exon_variant	2/2	3
TMEM37	ENST00000417645.1 linkuse as main transcript	c.*22C>A		downstream_gene_variant		3		ENSP00000400770.1	C9J1Q8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000180

AC:

AN:

55672

Hom.:

AF XY:

0.0000342

AC XY:

AN XY:

29200

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000193

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

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

Apr 15, 2024

The c.205C>A (p.Q69K) alteration is located in exon 2 (coding exon 2) of the TMEM37 gene. This alteration results from a C to A substitution at nucleotide position 205, causing the glutamine (Q) at amino acid position 69 to be replaced by a lysine (K). 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

0.089

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.46

DEOGEN2

Benign

0.20

.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;M

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.083

Sift

Benign

0.52

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.018

.;B

Vest4

0.12

MVP

0.26

MPC

0.46

ClinPred

0.95

GERP RS

3.6

Varity_R

0.089

gMVP

0.12

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