Variant 16-81999506-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_145168.3(SDR42E1):c.787T>A(p.Phe263Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SDR42E1
NM_145168.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SDR42E1	NM_145168.3 linkuse as main transcript	c.787T>A	p.Phe263Ile	missense_variant	3/3	ENST00000328945.7	NP_660151.2
SDR42E1	XM_005256257.5 linkuse as main transcript	c.787T>A	p.Phe263Ile	missense_variant	4/4		XP_005256314.1
SDR42E1	XM_011523471.4 linkuse as main transcript	c.778T>A	p.Phe260Ile	missense_variant	3/3		XP_011521773.1
SDR42E1	XM_047434925.1 linkuse as main transcript	c.778T>A	p.Phe260Ile	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.787T>A	p.Phe263Ile	missense_variant	3/3	1	NM_145168.3	ENSP00000332407	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

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.:

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

May 09, 2023

The c.787T>A (p.F263I) alteration is located in exon 3 (coding exon 2) of the SDR42E1 gene. This alteration results from a T to A substitution at nucleotide position 787, causing the phenylalanine (F) at amino acid position 263 to be replaced by an isoleucine (I). 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

Pathogenic

0.78

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

0.70

MutationAssessor

Pathogenic

3.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.64

MutPred

0.68

Loss of stability (P = 0.2424);

MVP

0.64

MPC

0.062

ClinPred

1.0

GERP RS

5.3

Varity_R

0.91

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over