rs530109812

chr12-56934048-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_148897.3(SDR9C7):c.214C>T(p.Arg72Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R72Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SDR9C7 NM_148897.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.0450

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-56934048-G-A is Pathogenic according to our data. Variant chr12-56934048-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 430712.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDR9C7	NM_148897.3	c.214C>T	p.Arg72Trp	missense_variant	1/4	ENST00000293502.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDR9C7	ENST00000293502.2	c.214C>T	p.Arg72Trp	missense_variant	1/4	1	NM_148897.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251226 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135772

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727242

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74482

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ichthyosis, congenital, autosomal recessive 13 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.049	D
MutationAssessor	Pathogenic	3.3	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.19	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.93	P
Vest4		0.79
MutPred		0.56		Loss of disorder (P = 0.0157);
MVP		0.77
MPC		0.63
ClinPred		0.98	D
GERP RS		2.4
Varity_R		0.46
gMVP		0.55

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

Other links and lift over

dbSNP: rs530109812; hg19: chr12-57327832; COSMIC: COSV53288823;