rs641738

Variant names:

• chr19-54173068-T-A
• rs641738
• NM_144686.4:c.50A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-54173068-T-A
• chr19-54173068-T-C
• chr19-54173068-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144686.4(TMC4):​c.50A>T​(p.Glu17Val) 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. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMC4 NM_144686.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 459 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 (MetaRNN=0.06770602).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144686.4. 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
	TMC4	NM_144686.4	MANE Select	c.50A>T	p.Glu17Val	missense	Exon 1 of 15	NP_653287.2	A0A087WVI4
	TMC4	NM_001145303.3		c.50A>T	p.Glu17Val	missense	Exon 1 of 15	NP_001138775.2	A0A087WT65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC4	ENST00000619895.5	TSL:1 MANE Select	c.50A>T	p.Glu17Val	missense	Exon 1 of 15	ENSP00000479458.1	A0A087WVI4
	TMC4	ENST00000617472.4	TSL:1	c.50A>T	p.Glu17Val	missense	Exon 1 of 15	ENSP00000477627.1	A0A087WT65
	TMC4	ENST00000883974.1		c.50A>T	p.Glu17Val	missense	Exon 1 of 15	ENSP00000554033.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 96546

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.3
DEOGEN2	Benign	0.0092	T
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.068	T
PhyloP100		-1.1
Sift4G	Uncertain	0.032	D
Vest4		0.072
PromoterAI		-0.011	Neutral
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs641738; hg19: chr19-54676763;