2-119437075-A-AGTGTGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_183240.3(TMEM37):c.208_209insGTGTGC(p.Thr70delinsSerValPro) variant causes a protein altering change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 1,613,660 control chromosomes in the GnomAD database, including 606,389 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.89 (60088 hom., cov: 0)
  • Exomes 𝑓: 0.86 (546301 hom.)
• Consequence: TMEM37 NM_183240.3 protein_altering
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-119437075-A-AGTGTGC is Benign according to our data. Variant chr2-119437075-A-AGTGTGC is described in ClinVar as [Benign]. Clinvar id is 767819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM37	NM_183240.3	c.208_209insGTGTGC	p.Thr70delinsSerValPro	protein_altering_variant	2/2	ENST00000306406.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM37	ENST00000306406.5	c.208_209insGTGTGC	p.Thr70delinsSerValPro	protein_altering_variant	2/2	1	NM_183240.3	P2
TMEM37	ENST00000409826.1	c.244_245insGTGTGC	p.Thr82delinsSerValPro	protein_altering_variant	2/2	3		A2
TMEM37	ENST00000465296.1	n.348_349insGTGTGC		non_coding_transcript_exon_variant	2/2	3
TMEM37	ENST00000417645.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.888 AC: 134752 AN: 151698 Hom.: 60032 Cov.: 0

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.892

GnomAD3 exomes AF: 0.858 AC: 215387 AN: 250980 Hom.: 92732 AF XY: 0.860 AC XY: 116678 AN XY: 135678

Gnomad AFR exome AF: 0.959

Gnomad AMR exome AF: 0.781

Gnomad ASJ exome AF: 0.890

Gnomad EAS exome AF: 0.886

Gnomad SAS exome AF: 0.861

Gnomad FIN exome AF: 0.821

Gnomad NFE exome AF: 0.866

Gnomad OTH exome AF: 0.862

GnomAD4 exome AF: 0.864 AC: 1263225 AN: 1461844 Hom.: 546301 Cov.: 33 AF XY: 0.864 AC XY: 628405 AN XY: 727224

Gnomad4 AFR exome AF: 0.960

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.893

Gnomad4 EAS exome AF: 0.890

Gnomad4 SAS exome AF: 0.859

Gnomad4 FIN exome AF: 0.822

Gnomad4 NFE exome AF: 0.865

Gnomad4 OTH exome AF: 0.871

GnomAD4 genome AF: 0.888 AC: 134871 AN: 151816 Hom.: 60088 Cov.: 0 AF XY: 0.885 AC XY: 65647 AN XY: 74188

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.892

Alfa AF: 0.854 Hom.: 5099

Bravo AF: 0.893

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3217464; hg19: chr2-120194651; COSMIC: COSV50026716; COSMIC: COSV50026716;