rs58542926

Variant names:

• chr19-19268740-C-A
• rs58542926
• NM_001001524.3:c.499G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-19268740-C-A
• chr19-19268740-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001001524.3(TM6SF2):​c.499G>T​(p.Glu167*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TM6SF2 NM_001001524.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 970 publications found

Genes affected

TM6SF2 (HGNC:11861): (transmembrane 6 superfamily member 2) Enables identical protein binding activity. Involved in regulation of lipid metabolic process. Located in endoplasmic reticulum membrane and endoplasmic reticulum-Golgi intermediate compartment membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267629 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001524.3. 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
	TM6SF2	NM_001001524.3	MANE Select	c.499G>T	p.Glu167*	stop_gained	Exon 6 of 10	NP_001001524.2	Q9BZW4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM6SF2	ENST00000389363.5	TSL:1 MANE Select	c.499G>T	p.Glu167*	stop_gained	Exon 6 of 10	ENSP00000374014.2	Q9BZW4-1
	TM6SF2	ENST00000864053.1		c.499G>T	p.Glu167*	stop_gained	Exon 6 of 10	ENSP00000534112.1
	TM6SF2	ENST00000864049.1		c.469G>T	p.Glu157*	stop_gained	Exon 6 of 10	ENSP00000534108.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1334

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	40
DANN	Uncertain	0.99
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.91	D
PhyloP100		3.5
Vest4		0.76
GERP RS		5.0
Mutation Taster		=57/143	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.43		Position offset: 14

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

Other links and lift over

dbSNP: rs58542926; hg19: chr19-19379549; COSMIC: COSV66985113; COSMIC: COSV66985113;