Variant 16-81999560-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145168.3(SDR42E1):c.733C>T(p.His245Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SDR42E1
NM_145168.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

Variant links:

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]

SDR42E1 links:

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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=0.07962865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SDR42E1	NM_145168.3 linkuse as main transcript	c.733C>T	p.His245Tyr	missense_variant	3/3	ENST00000328945.7	NP_660151.2
SDR42E1	XM_005256257.5 linkuse as main transcript	c.733C>T	p.His245Tyr	missense_variant	4/4		XP_005256314.1
SDR42E1	XM_011523471.4 linkuse as main transcript	c.724C>T	p.His242Tyr	missense_variant	3/3		XP_011521773.1
SDR42E1	XM_047434925.1 linkuse as main transcript	c.724C>T	p.His242Tyr	missense_variant	3/3		XP_047290881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDR42E1	ENST00000328945.7 linkuse as main transcript	c.733C>T	p.His245Tyr	missense_variant	3/3	1	NM_145168.3	ENSP00000332407	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727222

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:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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

Aug 05, 2023

The c.733C>T (p.H245Y) alteration is located in exon 3 (coding exon 2) of the SDR42E1 gene. This alteration results from a C to T substitution at nucleotide position 733, causing the histidine (H) at amino acid position 245 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.47

DEOGEN2

Benign

0.084

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.79

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.72

M_CAP

Benign

0.023

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.52

MutationTaster

Benign

0.88

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.33

REVEL

Benign

0.15

Sift

Benign

0.78

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.062

MutPred

0.56

Loss of catalytic residue at H245 (P = 0.0171);

MVP

0.28

MPC

0.010

ClinPred

0.039

GERP RS

-0.37

Varity_R

0.038

gMVP

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over