rs1595507495

Variant names:

• chr14-81489277-T-A
• NM_005065.6:c.1370A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-81489277-T-A
• chr14-81489277-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005065.6(SEL1L):​c.1370A>T​(p.Tyr457Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SEL1L NM_005065.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.95

Genes affected

SEL1L (HGNC:10717): (SEL1L adaptor subunit of SYVN1 ubiquitin ligase) The protein encoded by this gene is part of a protein complex required for the retrotranslocation or dislocation of misfolded proteins from the endoplasmic reticulum lumen to the cytosol, where they are degraded by the proteasome in a ubiquitin-dependent manner. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEL1L	NM_005065.6	c.1370A>T	p.Tyr457Phe	missense_variant	Exon 14 of 21	ENST00000336735.9	NP_005056.3
SEL1L	XM_005267988.4	c.1307A>T	p.Tyr436Phe	missense_variant	Exon 14 of 21		XP_005268045.1
SEL1L	XM_005267989.5	c.1301A>T	p.Tyr434Phe	missense_variant	Exon 13 of 20		XP_005268046.1
SEL1L	XM_047431676.1	c.1238A>T	p.Tyr413Phe	missense_variant	Exon 13 of 20		XP_047287632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEL1L	ENST00000336735.9	c.1370A>T	p.Tyr457Phe	missense_variant	Exon 14 of 21	1	NM_005065.6	ENSP00000337053.4
SEL1L	ENST00000555923.1	n.124A>T		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461812 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Benign	1.9	L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.052	T
Polyphen		0.99	D
Vest4		0.56
MutPred		0.79		Gain of methylation at R461 (P = 0.1751);
MVP		0.43
MPC		1.2
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.51
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-81955621;