Variant 2-119437097-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_183240.3(TMEM37):c.230G>A(p.Gly77Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,614,008 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 131 hom., cov: 34)

Exomes 𝑓: 0.0032 ( 131 hom. )

Consequence

TMEM37
NM_183240.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.363

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022252202).

BP6

Variant 2-119437097-G-A is Benign according to our data. Variant chr2-119437097-G-A is described in ClinVar as [Benign]. Clinvar id is 780835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM37	NM_183240.3 linkuse as main transcript	c.230G>A	p.Gly77Asp	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.230G>A	p.Gly77Asp	missense_variant	2/2	1	NM_183240.3	ENSP00000303148.4	Q8WXS4
TMEM37	ENST00000409826.1 linkuse as main transcript	c.266G>A	p.Gly89Asp	missense_variant	2/2	3		ENSP00000387015.1	E7EMC0
TMEM37	ENST00000465296.1 linkuse as main transcript	n.370G>A		non_coding_transcript_exon_variant	2/2	3
TMEM37	ENST00000417645.1 linkuse as main transcript	c.*47G>A		downstream_gene_variant		3		ENSP00000400770.1	C9J1Q8

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3678

AN:

152090

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00705

AC:

1768

AN:

250804

Hom.:

AF XY:

0.00546

AC XY:

741

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.0812

Gnomad AMR exome

AF:

0.00596

Gnomad ASJ exome

AF:

0.00576

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000882

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00325

AC:

4744

AN:

1461800

Hom.:

131

Cov.:

AF XY:

0.00291

AC XY:

2117

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0825

Gnomad4 AMR exome

AF:

0.00689

Gnomad4 ASJ exome

AF:

0.00536

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000803

Gnomad4 OTH exome

AF:

0.00730

GnomAD4 genome

AF:

0.0243

AC:

3692

AN:

152208

Hom.:

131

Cov.:

AF XY:

0.0229

AC XY:

1707

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0799

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00116

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.00368

Hom.:

Bravo

AF:

0.0284

ESP6500AA

AF:

0.0743

AC:

327

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00820

AC:

995

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.017

Sift

Benign

0.46

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.058

.;B

Vest4

0.28

MVP

0.088

MPC

0.54

ClinPred

0.0029

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.061

gMVP

0.11

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