chr19-54163825-G-A

Variant names:

• chr19-54163825-G-A
• NM_144686.4:c.1176C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_144686.4(TMC4):​c.1176C>T​(p.Ile392Ile) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 29)
• Consequence: TMC4 NM_144686.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.166
• Publications: 0 publications found

Genes affected

TMC4 (HGNC:22998): (transmembrane channel like 4) Predicted to enable mechanosensitive ion channel activity. Predicted to be involved in ion transmembrane transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 19-54163825-G-A is Benign according to our data. Variant chr19-54163825-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2681610.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.166 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC4	NM_144686.4	c.1176C>T	p.Ile392Ile	synonymous_variant	Exon 8 of 15	ENST00000619895.5	NP_653287.2
TMC4	NM_001145303.3	c.1194C>T	p.Ile398Ile	synonymous_variant	Exon 8 of 15		NP_001138775.2
TMC4	XR_935741.3	n.1237C>T		non_coding_transcript_exon_variant	Exon 8 of 15
TMC4	XM_011526486.3	c.816-666C>T		intron_variant	Intron 5 of 11		XP_011524788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC4	ENST00000619895.5	c.1176C>T	p.Ile392Ile	synonymous_variant	Exon 8 of 15	1	NM_144686.4	ENSP00000479458.1
TMC4	ENST00000617472.4	c.1194C>T	p.Ile398Ile	synonymous_variant	Exon 8 of 15	1		ENSP00000477627.1
TMC4	ENST00000613723.4	n.346C>T		non_coding_transcript_exon_variant	Exon 2 of 9	1
TMC4	ENST00000613492.4	n.486-666C>T		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1

-

Department of Clinical Pathology, School of Medicine, Fujita Health University

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.5
DANN	Benign	0.83
PhyloP100		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-54667557;