chr5-156951517-G-T

Position:

• chr5-156951517-G-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.674C>A​(p.Thr225Asn) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TIMD4 NM_138379.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54

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=0.15327021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TIMD4	NM_138379.3	c.674C>A	p.Thr225Asn	missense_variant	3/9	ENST00000274532.7
TIMD4	NM_001146726.2	c.674C>A	p.Thr225Asn	missense_variant	3/8
TIMD4	XM_017010021.2	c.674C>A	p.Thr225Asn	missense_variant	3/7
TIMD4	XM_011534694.3	c.674C>A	p.Thr225Asn	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIMD4	ENST00000274532.7	c.674C>A	p.Thr225Asn	missense_variant	3/9	1	NM_138379.3	P2
TIMD4	ENST00000407087.4	c.674C>A	p.Thr225Asn	missense_variant	3/8	2		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jan 23, 2023

The c.674C>A (p.T225N) alteration is located in exon 3 (coding exon 3) of the TIMD4 gene. This alteration results from a C to A substitution at nucleotide position 674, causing the threonine (T) at amino acid position 225 to be replaced by an asparagine (N). 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	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.023
Sift	Benign	0.038	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.24	B;.
Vest4		0.42
MutPred		0.24		Loss of glycosylation at T225 (P = 0.0067);Loss of glycosylation at T225 (P = 0.0067);
MVP		0.26
MPC		0.17
ClinPred		0.24	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.47

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: chr5-156378528;