chr16-81999940-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_145168.3(SDR42E1):c.353T>C(p.Leu118Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
SDR42E1
NM_145168.3 missense
NM_145168.3 missense
Scores
13
3
3
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
SDR42E1 (HGNC:29834): (short chain dehydrogenase/reductase family 42E, member 1) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Predicted to be involved in steroid biosynthetic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.957
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SDR42E1 | NM_145168.3 | c.353T>C | p.Leu118Ser | missense_variant | 3/3 | ENST00000328945.7 | |
SDR42E1 | XM_005256257.5 | c.353T>C | p.Leu118Ser | missense_variant | 4/4 | ||
SDR42E1 | XM_011523471.4 | c.344T>C | p.Leu115Ser | missense_variant | 3/3 | ||
SDR42E1 | XM_047434925.1 | c.344T>C | p.Leu115Ser | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SDR42E1 | ENST00000328945.7 | c.353T>C | p.Leu118Ser | missense_variant | 3/3 | 1 | NM_145168.3 | P1 | |
SDR42E1 | ENST00000532128.5 | c.344T>C | p.Leu115Ser | missense_variant | 4/4 | 5 | |||
SDR42E1 | ENST00000534209.1 | n.686T>C | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000521 AC: 13AN: 249584Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135408
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461584Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727098
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74336
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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 | Jul 25, 2023 | The c.353T>C (p.L118S) alteration is located in exon 3 (coding exon 2) of the SDR42E1 gene. This alteration results from a T to C substitution at nucleotide position 353, causing the leucine (L) at amino acid position 118 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of stability (P = 0.0175);.;
MVP
MPC
ClinPred
D
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