chr5-156922161-A-C

Variant names:

• chr5-156922161-A-C
• rs779642915
• NM_138379.3:c.950T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138379.3(TIMD4):​c.950T>G​(p.Met317Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TIMD4 NM_138379.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

Genes affected

TIMD4 (HGNC:25132): (T cell immunoglobulin and mucin domain containing 4) Predicted to enable phosphatidylserine binding activity. Predicted to act upstream of or within apoptotic cell clearance. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35841346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMD4	NM_138379.3	c.950T>G	p.Met317Arg	missense_variant	Exon 7 of 9	ENST00000274532.7	NP_612388.2
TIMD4	NM_001146726.2	c.866T>G	p.Met289Arg	missense_variant	Exon 6 of 8		NP_001140198.1
TIMD4	XM_017010021.2	c.785T>G	p.Met262Arg	missense_variant	Exon 5 of 7		XP_016865510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMD4	ENST00000274532.7	c.950T>G	p.Met317Arg	missense_variant	Exon 7 of 9	1	NM_138379.3	ENSP00000274532.2
TIMD4	ENST00000407087.4	c.866T>G	p.Met289Arg	missense_variant	Exon 6 of 8	2		ENSP00000385973.3
TIMD4	ENST00000406964.5	c.56T>G	p.Met19Arg	missense_variant	Exon 3 of 5	2		ENSP00000385882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N;D;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.017	D;D;D
Sift4G	Benign	0.18	T;D;T
Polyphen		0.62	P;.;.
Vest4		0.65
MutPred		0.39		Loss of sheet (P = 0.007);.;.;
MVP		0.44
MPC		0.23
ClinPred		0.26	T
GERP RS		4.1
Varity_R		0.34
gMVP		0.41

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: rs779642915; hg19: chr5-156349172;