chr12-56929422-C-T

Variant names:

• chr12-56929422-C-T
• rs75997315
• NM_148897.3:c.692G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_148897.3(SDR9C7):​c.692G>A​(p.Arg231Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,612,416 control chromosomes in the GnomAD database, including 72 homozygotes. 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R231W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.011 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (36 hom.)
• Consequence: SDR9C7 NM_148897.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0120
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• ichthyosis, congenital, autosomal recessive 13

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019102693).
• BP6: Variant 12-56929422-C-T is Benign according to our data. Variant chr12-56929422-C-T is described in ClinVar as Benign. ClinVar VariationId is 776722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0112 (1708/152270) while in subpopulation AFR AF = 0.0384 (1596/41546). AF 95% confidence interval is 0.0368. There are 36 homozygotes in GnomAd4. There are 829 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148897.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDR9C7	NM_148897.3	MANE Select	c.692G>A	p.Arg231Gln	missense	Exon 3 of 4	NP_683695.1	Q8NEX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDR9C7	ENST00000293502.2	TSL:1 MANE Select	c.692G>A	p.Arg231Gln	missense	Exon 3 of 4	ENSP00000293502.1	Q8NEX9

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1697 AN: 152152 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00957

GnomAD2 exomes AF: 0.00295 AC: 742 AN: 251334 AF XY: 0.00218

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00126 AC: 1837 AN: 1460146 Hom.: 36 Cov.: 31 AF XY: 0.00111 AC XY: 803 AN XY: 725936

African (AFR) AF: 0.0421 AC: 1410 AN: 33464

American (AMR) AF: 0.00195 AC: 87 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5762

European-Non Finnish (NFE) AF: 0.0000765 AC: 85 AN: 1110530

Other (OTH) AF: 0.00343 AC: 207 AN: 60330

GnomAD4 genome AF: 0.0112 AC: 1708 AN: 152270 Hom.: 36 Cov.: 32 AF XY: 0.0111 AC XY: 829 AN XY: 74444

African (AFR) AF: 0.0384 AC: 1596 AN: 41546

American (AMR) AF: 0.00556 AC: 85 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68010

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.00396 Hom.: 23

Bravo AF: 0.0132

ESP6500AA AF: 0.0386 AC: 170

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00348 AC: 422

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.012
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.15
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.026	B
Vest4		0.33
MVP		0.79
MPC		0.19
ClinPred		0.017	T
GERP RS		3.6
Varity_R		0.081
gMVP		0.50
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs75997315; hg19: chr12-57323206;