chr14-24290887-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001136050.3(DHRS1):c.914T>C(p.Ile305Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
DHRS1
NM_001136050.3 missense
NM_001136050.3 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 2.15
Genes affected
DHRS1 (HGNC:16445): (dehydrogenase/reductase 1) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family. The encoded enzyme contains a conserved catalytic domain and likely functions as an oxidoreductase. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.14302123).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHRS1 | NM_001136050.3 | c.914T>C | p.Ile305Thr | missense_variant | 9/9 | ENST00000288111.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHRS1 | ENST00000288111.12 | c.914T>C | p.Ile305Thr | missense_variant | 9/9 | 1 | NM_001136050.3 | P1 | |
ENST00000669726.3 | n.111-7727A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151792Hom.: 0 Cov.: 30
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251462Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135902
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GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461870Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24AN XY: 727232
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151910Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2AN XY: 74274
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2023 | The c.914T>C (p.I305T) alteration is located in exon 9 (coding exon 8) of the DHRS1 gene. This alteration results from a T to C substitution at nucleotide position 914, causing the isoleucine (I) at amino acid position 305 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at