chr5-156926310-A-T

Position:

• chr5-156926310-A-T

Variant summary

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

The NM_138379.3(TIMD4):​c.847T>A​(p.Ser283Thr) variant causes a missense, splice region 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. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TIMD4 NM_138379.3 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.107

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=0.102151066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIMD4	NM_138379.3	c.847T>A	p.Ser283Thr	missense_variant, splice_region_variant	6/9	ENST00000274532.7
TIMD4	NM_001146726.2	c.763T>A	p.Ser255Thr	missense_variant, splice_region_variant	5/8
TIMD4	XM_017010021.2	c.682T>A	p.Ser228Thr	missense_variant, splice_region_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMD4	ENST00000274532.7	c.847T>A	p.Ser283Thr	missense_variant, splice_region_variant	6/9	1	NM_138379.3	P2
TIMD4	ENST00000407087.4	c.763T>A	p.Ser255Thr	missense_variant, splice_region_variant	5/8	2		A2
TIMD4	ENST00000406964.5	c.-48T>A		splice_region_variant, 5_prime_UTR_variant	2/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.847T>A (p.S283T) alteration is located in exon 6 (coding exon 6) of the TIMD4 gene. This alteration results from a T to A substitution at nucleotide position 847, causing the serine (S) at amino acid position 283 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.97
DANN	Benign	0.48
DEOGEN2	Benign	0.024	T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.11	N;N
REVEL	Benign	0.12
Sift	Benign	0.33	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.90	P;.
Vest4		0.061
MutPred		0.073		Gain of glycosylation at S283 (P = 0.0489);.;
MVP		0.36
MPC		0.091
ClinPred		0.54	D
GERP RS		-2.9
Varity_R		0.049
gMVP		0.095

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-156353321;