chr19-54073982-T-C

Position:

• chr19-54073982-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135686.3(TARM1):​c.596A>G​(p.Tyr199Cys) 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. 11/18 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: TARM1 NM_001135686.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.895

Genes affected

TARM1 (HGNC:37250): (T cell-interacting, activating receptor on myeloid cells 1) Enables immunoglobulin receptor binding activity. Involved in negative regulation of CD4-positive, alpha-beta T cell activation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2994839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TARM1	NM_001135686.3	c.596A>G	p.Tyr199Cys	missense_variant	4/5	ENST00000432826.2
TARM1	NM_001330650.1	c.620A>G	p.Tyr207Cys	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TARM1	ENST00000432826.2	c.596A>G	p.Tyr199Cys	missense_variant	4/5	1	NM_001135686.3	P2
TARM1	ENST00000616041.4	c.620A>G	p.Tyr207Cys	missense_variant	4/5	2		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000649 AC: 1 AN: 154068 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81760

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000917

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Sep 14, 2023

The c.596A>G (p.Y199C) alteration is located in exon 4 (coding exon 4) of the TARM1 gene. This alteration results from a A to G substitution at nucleotide position 596, causing the tyrosine (Y) at amino acid position 199 to be replaced by a cysteine (C). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.78	T;.
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.31	T
Sift4G	Uncertain	0.023	D;D
Vest4		0.38
MutPred		0.44		.;Gain of catalytic residue at M197 (P = 0.042);
MVP		0.21
ClinPred		0.96	D
GERP RS		-0.97
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

LitVar

Other links and lift over

dbSNP: rs1162899950; hg19: chr19-54577234;