2-119437328-C-T

Position:

• chr2-119437328-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_183240.3(TMEM37):​c.461C>T​(p.Thr154Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TMEM37 NM_183240.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM37	NM_183240.3	c.461C>T	p.Thr154Ile	missense_variant	2/2	ENST00000306406.5	NP_899063.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM37	ENST00000306406.5	c.461C>T	p.Thr154Ile	missense_variant	2/2	1	NM_183240.3	ENSP00000303148.4
TMEM37	ENST00000409826.1	c.497C>T	p.Thr166Ile	missense_variant	2/2	3		ENSP00000387015.1
TMEM37	ENST00000465296.1	n.601C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.461C>T (p.T154I) alteration is located in exon 2 (coding exon 2) of the TMEM37 gene. This alteration results from a C to T substitution at nucleotide position 461, causing the threonine (T) at amino acid position 154 to be replaced by an isoleucine (I). 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	0.30
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	.;D
Eigen	Benign	0.19
Eigen_PC	Benign	0.071
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.4	D;D
REVEL	Benign	0.093
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.99	.;D
Vest4		0.75
MutPred		0.28		.;Loss of helix (P = 0.1299);
MVP		0.34
MPC		0.77
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.12
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-120194904;