12-56929396-G-A

Position:

chr12-56929396-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The ENST00000293502.2(SDR9C7):c.718C>T(p.Arg240Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,597,288 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

SDR9C7
ENST00000293502.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: -1.16

Variant links:

Genes affected

SDR9C7 (HGNC:29958): (short chain dehydrogenase/reductase family 9C member 7) This gene encodes a protein with similarity to the short-chain dehydrogenase/reductase (SDR) family but has not been shown to have retinoid or dehydrogenase activities. [provided by RefSeq, Apr 2010]

SDR9C7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0059093237).

BP6

Variant 12-56929396-G-A is Benign according to our data. Variant chr12-56929396-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1800780.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00122 (186/152210) while in subpopulation AFR AF= 0.00405 (168/41528). AF 95% confidence interval is 0.00355. There are 0 homozygotes in gnomad4. There are 87 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDR9C7	NM_148897.3 linkuse as main transcript	c.718C>T	p.Arg240Cys	missense_variant	3/4	ENST00000293502.2	NP_683695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDR9C7	ENST00000293502.2 linkuse as main transcript	c.718C>T	p.Arg240Cys	missense_variant	3/4	1	NM_148897.3	ENSP00000293502	P1

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

186

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00406

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000458

AC:

115

AN:

251126

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.00474

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000213

AC:

308

AN:

1445078

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

157

AN XY:

714582

show subpopulations

Gnomad4 AFR exome

AF:

0.00344

Gnomad4 AMR exome

AF:

0.000315

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.000698

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000929

Gnomad4 OTH exome

AF:

0.000285

GnomAD4 genome

AF:

0.00122

AC:

186

AN:

152210

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.00405

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.00140

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 24, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Nov 15, 2022	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.718C>T (p.R240C) alteration is located in exon 3 (coding exon 3) of the SDR9C7 gene. This alteration results from a C to T substitution at nucleotide position 718, causing the arginine (R) at amino acid position 240 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.19

M_CAP

Benign

0.073

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.22

Sift

Benign

0.041

Sift4G

Uncertain

0.022

Polyphen

0.0040

Vest4

0.26

MVP

0.75

MPC

0.22

ClinPred

0.021

GERP RS

3.5

Varity_R

0.087

gMVP

0.50

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