chr5-156951517-G-T

Variant names:

• chr5-156951517-G-T
• NM_138379.3:c.674C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15327021).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138379.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMD4	NM_138379.3	MANE Select	c.674C>A	p.Thr225Asn	missense	Exon 3 of 9	NP_612388.2	Q96H15-1
	TIMD4	NM_001146726.2		c.674C>A	p.Thr225Asn	missense	Exon 3 of 8	NP_001140198.1	Q96H15-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMD4	ENST00000274532.7	TSL:1 MANE Select	c.674C>A	p.Thr225Asn	missense	Exon 3 of 9	ENSP00000274532.2	Q96H15-1
	TIMD4	ENST00000407087.4	TSL:2	c.674C>A	p.Thr225Asn	missense	Exon 3 of 8	ENSP00000385973.3	Q96H15-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.023
Sift	Benign	0.038	D
Sift4G	Benign	0.14	T
Polyphen		0.24	B
Vest4		0.42
MutPred		0.24		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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr5-156378528;