rs2227956
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005527.4(HSPA1L):c.1478C>T(p.Thr493Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 1,613,352 control chromosomes in the GnomAD database, including 566,847 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T493K) has been classified as Uncertain significance.
Frequency
Consequence
NM_005527.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSPA1L | NM_005527.4 | c.1478C>T | p.Thr493Met | missense_variant | 2/2 | ENST00000375654.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSPA1L | ENST00000375654.5 | c.1478C>T | p.Thr493Met | missense_variant | 2/2 | 1 | NM_005527.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.877 AC: 133293AN: 152002Hom.: 58760 Cov.: 31
GnomAD3 exomes AF: 0.866 AC: 217175AN: 250884Hom.: 94552 AF XY: 0.864 AC XY: 117222AN XY: 135624
GnomAD4 exome AF: 0.832 AC: 1216116AN: 1461232Hom.: 508026 Cov.: 62 AF XY: 0.835 AC XY: 606890AN XY: 726950
GnomAD4 genome AF: 0.877 AC: 133414AN: 152120Hom.: 58821 Cov.: 31 AF XY: 0.878 AC XY: 65247AN XY: 74346
ClinVar
Submissions by phenotype
HSPA1L-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 21, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at