5-156951682-G-T

Variant names:

• chr5-156951682-G-T
• rs61743250
• NM_138379.3:c.509C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138379.3(TIMD4):​c.509C>A​(p.Thr170Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,614,054 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (231 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (200 hom.)
• Consequence: TIMD4 NM_138379.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38
• Publications: 3 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022141933).
• BP6: Variant 5-156951682-G-T is Benign according to our data. Variant chr5-156951682-G-T is described in ClinVar as Benign. ClinVar VariationId is 780591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

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.509C>A	p.Thr170Lys	missense	Exon 3 of 9	NP_612388.2	Q96H15-1
	TIMD4	NM_001146726.2		c.509C>A	p.Thr170Lys	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.509C>A	p.Thr170Lys	missense	Exon 3 of 9	ENSP00000274532.2	Q96H15-1
	TIMD4	ENST00000407087.4	TSL:2	c.509C>A	p.Thr170Lys	missense	Exon 3 of 8	ENSP00000385973.3	Q96H15-2

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4380 AN: 152052 Hom.: 231 Cov.: 31

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.00756 AC: 1901 AN: 251486 AF XY: 0.00572

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.00497

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00301 AC: 4407 AN: 1461886 Hom.: 200 Cov.: 31 AF XY: 0.00256 AC XY: 1861 AN XY: 727248

African (AFR) AF: 0.106 AC: 3542 AN: 33478

American (AMR) AF: 0.00593 AC: 265 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.000152 AC: 169 AN: 1112008

Other (OTH) AF: 0.00652 AC: 394 AN: 60394

GnomAD4 genome AF: 0.0289 AC: 4397 AN: 152168 Hom.: 231 Cov.: 31 AF XY: 0.0284 AC XY: 2111 AN XY: 74408

African (AFR) AF: 0.101 AC: 4168 AN: 41472

American (AMR) AF: 0.0101 AC: 154 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68010

Other (OTH) AF: 0.0237 AC: 50 AN: 2112

Alfa AF: 0.0100 Hom.: 131

Bravo AF: 0.0336

ESP6500AA AF: 0.0969 AC: 427

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00934 AC: 1134

Asia WGS AF: 0.00635 AC: 23 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.4
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.082
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.97	D
Vest4		0.44
MVP		0.31
MPC		0.35
ClinPred		0.036	T
GERP RS		3.3
Varity_R		0.18
gMVP		0.61
Mutation Taster		=95/5	polymorphism (auto)

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: rs61743250; hg19: chr5-156378693;