2-119431916-G-T

Variant names:

• chr2-119431916-G-T
• rs13016450
• NM_183240.3:c.13G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_183240.3(TMEM37):​c.13G>T​(p.Gly5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000931 in 1,073,812 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G5R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: TMEM37 NM_183240.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183240.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM37	NM_183240.3	MANE Select	c.13G>T	p.Gly5Cys	missense	Exon 1 of 2	NP_899063.2	Q8WXS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM37	ENST00000306406.5	TSL:1 MANE Select	c.13G>T	p.Gly5Cys	missense	Exon 1 of 2	ENSP00000303148.4	Q8WXS4
	TMEM37	ENST00000911072.1		c.13G>T	p.Gly5Cys	missense	Exon 1 of 3	ENSP00000581131.1
	TMEM37	ENST00000933286.1		c.13G>T	p.Gly5Cys	missense	Exon 1 of 2	ENSP00000603345.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.31e-7 AC: 1 AN: 1073812 Hom.: 0 Cov.: 32 AF XY: 0.00000197 AC XY: 1 AN XY: 507490

African (AFR) AF: 0.00 AC: 0 AN: 22550

American (AMR) AF: 0.00 AC: 0 AN: 8120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14004

East Asian (EAS) AF: 0.00 AC: 0 AN: 25950

South Asian (SAS) AF: 0.0000504 AC: 1 AN: 19846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2884

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 916266

Other (OTH) AF: 0.00 AC: 0 AN: 43078

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.38	T
M_CAP	Pathogenic	0.69	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.087
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.028	D
Polyphen		0.98	D
Vest4		0.19
MutPred		0.40		Loss of disorder (P = 0.0104)
MVP		0.27
MPC		0.80
ClinPred		0.95	D
GERP RS		3.6
PromoterAI		0.0062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.24
gMVP		0.25
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs13016450; hg19: chr2-120189492;