rs765431768

Variant names:

• chr19-54161156-G-A
• rs765431768
• NM_144686.4:c.1791C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-54161156-G-A
• chr19-54161156-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144686.4(TMC4):​c.1791C>T​(p.Ser597Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,436,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TMC4 NM_144686.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.15

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-4.15 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMC4	NM_144686.4	c.1791C>T	p.Ser597Ser	synonymous_variant	Exon 12 of 15	ENST00000619895.5	NP_653287.2
TMC4	NM_001145303.3	c.1809C>T	p.Ser603Ser	synonymous_variant	Exon 12 of 15		NP_001138775.2
TMC4	XM_011526486.3	c.1329C>T	p.Ser443Ser	synonymous_variant	Exon 9 of 12		XP_011524788.1
TMC4	XR_935741.3	n.1852C>T		non_coding_transcript_exon_variant	Exon 12 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMC4	ENST00000619895.5	c.1791C>T	p.Ser597Ser	synonymous_variant	Exon 12 of 15	1	NM_144686.4	ENSP00000479458.1
TMC4	ENST00000617472.4	c.1809C>T	p.Ser603Ser	synonymous_variant	Exon 12 of 15	1		ENSP00000477627.1
TMC4	ENST00000613723.4	n.1032C>T		non_coding_transcript_exon_variant	Exon 6 of 9	1
TMC4	ENST00000615945.4	n.-184C>T		upstream_gene_variant		2		ENSP00000481392.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000444 AC: 1 AN: 225350 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000186

GnomAD4 exome AF: 0.00000278 AC: 4 AN: 1436446 Hom.: 0 Cov.: 39 AF XY: 0.00000280 AC XY: 2 AN XY: 713476

African (AFR) AF: 0.00 AC: 0 AN: 31840

American (AMR) AF: 0.00 AC: 0 AN: 38066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39344

South Asian (SAS) AF: 0.00 AC: 0 AN: 83340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52766

Middle Eastern (MID) AF: 0.000355 AC: 2 AN: 5636

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101416

Other (OTH) AF: 0.0000169 AC: 1 AN: 59120

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.92
PhyloP100		-4.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs765431768; hg19: chr19-54664893;