rs1422018680

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_031463.5(HSDL1):​c.826G>T​(p.Ala276Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A276T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HSDL1
NM_031463.5 missense

Scores

3
12
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.65
Variant links:
Genes affected
HSDL1 (HGNC:16475): (hydroxysteroid dehydrogenase like 1) Predicted to enable oxidoreductase activity. Located in intermediate filament cytoskeleton and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSDL1NM_031463.5 linkc.826G>T p.Ala276Ser missense_variant Exon 5 of 6 ENST00000219439.9 NP_113651.4 Q3SXM5-1I6L975
HSDL1NM_001146051.2 linkc.661G>T p.Ala221Ser missense_variant Exon 6 of 7 NP_001139523.1 Q3SXM5-2I6L975
HSDL1XM_005256189.4 linkc.826G>T p.Ala276Ser missense_variant Exon 5 of 6 XP_005256246.1 Q3SXM5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSDL1ENST00000219439.9 linkc.826G>T p.Ala276Ser missense_variant Exon 5 of 6 1 NM_031463.5 ENSP00000219439.4 Q3SXM5-1
HSDL1ENST00000434463.7 linkc.661G>T p.Ala221Ser missense_variant Exon 6 of 7 2 ENSP00000407437.3 Q3SXM5-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727248
show subpopulations
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
0.16
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.82
T;T
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Uncertain
0.66
D
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Uncertain
0.58
Sift
Uncertain
0.011
D;D
Sift4G
Uncertain
0.021
D;D
Polyphen
0.97
D;.
Vest4
0.72
MutPred
0.62
Gain of disorder (P = 0.0361);.;
MVP
0.94
MPC
0.12
ClinPred
0.97
D
GERP RS
5.3
Varity_R
0.37
gMVP
0.68

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: chr16-84163221; API