rs1225994470

Variant names:

• chr5-156920495-T-A
• NM_138379.3:c.1021A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-156920495-T-A
• chr5-156920495-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138379.3(TIMD4):​c.1021A>T​(p.Met341Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TIMD4 NM_138379.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07226032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMD4	NM_138379.3	c.1021A>T	p.Met341Leu	missense_variant	Exon 8 of 9	ENST00000274532.7	NP_612388.2
TIMD4	NM_001146726.2	c.937A>T	p.Met313Leu	missense_variant	Exon 7 of 8		NP_001140198.1
TIMD4	XM_017010021.2	c.856A>T	p.Met286Leu	missense_variant	Exon 6 of 7		XP_016865510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMD4	ENST00000274532.7	c.1021A>T	p.Met341Leu	missense_variant	Exon 8 of 9	1	NM_138379.3	ENSP00000274532.2
TIMD4	ENST00000407087.4	c.937A>T	p.Met313Leu	missense_variant	Exon 7 of 8	2		ENSP00000385973.3
TIMD4	ENST00000406964.5	c.127A>T	p.Met43Leu	missense_variant	Exon 4 of 5	2		ENSP00000385882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461722 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.9
DANN	Benign	0.74
DEOGEN2	Benign	0.049	T;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.36	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.80	N;N;N
REVEL	Benign	0.032
Sift	Benign	0.049	D;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.52	P;.;.
Vest4		0.21
MutPred		0.23		Gain of sheet (P = 0.1208);.;.;
MVP		0.25
MPC		0.055
ClinPred		0.12	T
GERP RS		1.8
Varity_R		0.18
gMVP		0.076

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: chr5-156347506;