chr5-156922161-A-G

Variant names:

• chr5-156922161-A-G
• rs779642915
• NM_138379.3:c.950T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138379.3(TIMD4):​c.950T>C​(p.Met317Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TIMD4 NM_138379.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.058403134).

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.950T>C	p.Met317Thr	missense	Exon 7 of 9	NP_612388.2	Q96H15-1
	TIMD4	NM_001146726.2		c.866T>C	p.Met289Thr	missense	Exon 6 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.950T>C	p.Met317Thr	missense	Exon 7 of 9	ENSP00000274532.2	Q96H15-1
	TIMD4	ENST00000407087.4	TSL:2	c.866T>C	p.Met289Thr	missense	Exon 6 of 8	ENSP00000385973.3	Q96H15-2
	TIMD4	ENST00000406964.5	TSL:2	c.56T>C	p.Met19Thr	missense	Exon 3 of 5	ENSP00000385882.1	B5MCV9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250952 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461756 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 727176

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111940

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000247 AC: 3

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	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.055	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.7
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.16
Sift	Benign	0.33	T
Sift4G	Benign	0.53	T
Polyphen		0.65	P
Vest4		0.28
MutPred		0.36		Loss of stability (P = 0.0274)
MVP		0.38
MPC		0.060
ClinPred		0.080	T
GERP RS		4.1
Varity_R		0.051
gMVP		0.22
Mutation Taster		=93/7	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

dbSNP: rs779642915; hg19: chr5-156349172;