5-156951635-T-A

Variant names:

• chr5-156951635-T-A
• rs184214058
• NM_138379.3:c.556A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138379.3(TIMD4):​c.556A>T​(p.Thr186Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: TIMD4 NM_138379.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056462556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMD4	NM_138379.3	c.556A>T	p.Thr186Ser	missense_variant	Exon 3 of 9	ENST00000274532.7	NP_612388.2
TIMD4	NM_001146726.2	c.556A>T	p.Thr186Ser	missense_variant	Exon 3 of 8		NP_001140198.1
TIMD4	XM_017010021.2	c.556A>T	p.Thr186Ser	missense_variant	Exon 3 of 7		XP_016865510.1
TIMD4	XM_011534694.3	c.556A>T	p.Thr186Ser	missense_variant	Exon 3 of 6		XP_011532996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMD4	ENST00000274532.7	c.556A>T	p.Thr186Ser	missense_variant	Exon 3 of 9	1	NM_138379.3	ENSP00000274532.2
TIMD4	ENST00000407087.4	c.556A>T	p.Thr186Ser	missense_variant	Exon 3 of 8	2		ENSP00000385973.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.068
DANN	Benign	0.38
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.016
Sift	Benign	0.80	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0020	B;.
Vest4		0.087
MutPred		0.26		Gain of glycosylation at T186 (P = 0.0719);Gain of glycosylation at T186 (P = 0.0719);
MVP		0.11
MPC		0.049
ClinPred		0.040	T
GERP RS		2.3
Varity_R		0.041
gMVP		0.27

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: rs184214058; hg19: chr5-156378646;