2-119433855-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183240.3(TMEM37):c.21+1931T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 152,170 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.034 (110 hom., cov: 32)
• Consequence: TMEM37 NM_183240.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.059 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM37	NM_183240.3	c.21+1931T>C		intron_variant		ENST00000306406.5
TMEM37	XM_006712300.4	c.-241+1605T>C		intron_variant
TMEM37	XM_011510659.3	c.58-3034T>C		intron_variant
TMEM37	XM_047443445.1	c.-241+2270T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM37	ENST00000306406.5	c.21+1931T>C		intron_variant		1	NM_183240.3	P2
TMEM37	ENST00000409826.1	c.58-3034T>C		intron_variant		3		A2
TMEM37	ENST00000417645.1	c.39-3034T>C		intron_variant		3
TMEM37	ENST00000465296.1	n.161+1605T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5126 AN: 152052 Hom.: 109 Cov.: 32

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0251

Gnomad OTH AF: 0.0292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0337 AC: 5135 AN: 152170 Hom.: 110 Cov.: 32 AF XY: 0.0335 AC XY: 2492 AN XY: 74408

Gnomad4 AFR AF: 0.0610

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0544

Gnomad4 FIN AF: 0.0201

Gnomad4 NFE AF: 0.0251

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0234 Hom.: 43

Bravo AF: 0.0341

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.3
Dann	Benign	0.59

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

Other links and lift over

dbSNP: rs17015803; hg19: chr2-120191431;