NM_148897.3:c.802A>G

Variant names:

• chr12-56923973-T-C
• rs1955715756
• NM_148897.3:c.802A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_148897.3(SDR9C7):​c.802A>G​(p.Ile268Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDR9C7 NM_148897.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0160
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06539562).
• BP6: Variant 12-56923973-T-C is Benign according to our data. Variant chr12-56923973-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2596924.Status of the report is criteria_provided_single_submitter, 1 stars.

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.802A>G	p.Ile268Val	missense	Exon 4 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.802A>G	p.Ile268Val	missense	Exon 4 of 4	ENSP00000293502.1	Q8NEX9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	2.6
DANN	Benign	0.72
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.016
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.17
Sift	Benign	0.082	T
Sift4G	Benign	0.083	T
Polyphen		0.0010	B
Vest4		0.015
MutPred		0.61		Loss of catalytic residue at V269 (P = 0.0763)
MVP		0.63
MPC		0.13
ClinPred		0.044	T
GERP RS		-3.4
Varity_R		0.043
gMVP		0.36
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1955715756; hg19: chr12-57317757;