rs141557472

Variant names:

• chr5-156954433-G-A
• rs141557472
• NM_138379.3:c.382C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-156954433-G-A
• chr5-156954433-G-T

Variant summary

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

The NM_138379.3(TIMD4):​c.382C>T​(p.Arg128Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,474 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: TIMD4 NM_138379.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMD4	NM_138379.3	c.382C>T	p.Arg128Cys	missense_variant	Exon 2 of 9	ENST00000274532.7	NP_612388.2
TIMD4	NM_001146726.2	c.382C>T	p.Arg128Cys	missense_variant	Exon 2 of 8		NP_001140198.1
TIMD4	XM_017010021.2	c.382C>T	p.Arg128Cys	missense_variant	Exon 2 of 7		XP_016865510.1
TIMD4	XM_011534694.3	c.382C>T	p.Arg128Cys	missense_variant	Exon 2 of 6		XP_011532996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMD4	ENST00000274532.7	c.382C>T	p.Arg128Cys	missense_variant	Exon 2 of 9	1	NM_138379.3	ENSP00000274532.2
TIMD4	ENST00000407087.4	c.382C>T	p.Arg128Cys	missense_variant	Exon 2 of 8	2		ENSP00000385973.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000321 AC: 8 AN: 249464 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134840

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461474 Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12 AN XY: 727008

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000302

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.031	D;D
Polyphen		1.0	D;.
Vest4		0.36
MVP		0.26
MPC		0.38
ClinPred		0.64	D
GERP RS		3.7
Varity_R		0.28
gMVP		0.68

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: rs141557472; hg19: chr5-156381444; COSMIC: COSV50855913;