NM_002035.4:c.321+97A>G

Variant names:

• chr18-63355401-T-C
• rs1809319
• NM_002035.4:c.321+97A>G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3 BA1

The NM_002035.4(KDSR):​c.321+97A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,604,996 control chromosomes in the GnomAD database, including 336,579 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (29252 hom., cov: 32)
  • Exomes 𝑓: 0.65 (307327 hom.)
• Consequence: KDSR NM_002035.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

Genes affected

KDSR (HGNC:4021): (3-ketodihydrosphingosine reductase) The protein encoded by this gene catalyzes the reduction of 3-ketodihydrosphingosine to dihydrosphingosine. The putative active site residues of the encoded protein are found on the cytosolic side of the endoplasmic reticulum membrane. A chromosomal rearrangement involving this gene is a cause of follicular lymphoma, also known as type II chronic lymphatic leukemia. The mutation of a conserved residue in the bovine ortholog causes spinal muscular atrophy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDSR	NM_002035.4	c.321+97A>G		intron_variant	Intron 4 of 9	ENST00000645214.2	NP_002026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDSR	ENST00000645214.2	c.321+97A>G		intron_variant	Intron 4 of 9		NM_002035.4	ENSP00000494352.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93804 AN: 151972 Hom.: 29243 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.624

GnomAD4 exome AF: 0.649 AC: 943044 AN: 1452906 Hom.: 307327 Cov.: 34 AF XY: 0.650 AC XY: 469745 AN XY: 722508

Gnomad4 AFR exome AF: 0.538

Gnomad4 AMR exome AF: 0.618

Gnomad4 ASJ exome AF: 0.608

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.660

Gnomad4 NFE exome AF: 0.659

Gnomad4 OTH exome AF: 0.632

GnomAD4 genome AF: 0.617 AC: 93839 AN: 152090 Hom.: 29252 Cov.: 32 AF XY: 0.615 AC XY: 45728 AN XY: 74352

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.619

Alfa AF: 0.634 Hom.: 28215

Bravo AF: 0.606

Asia WGS AF: 0.548 AC: 1908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.61		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.61		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1809319; hg19: chr18-61022634; COSMIC: COSV58506496; COSMIC: COSV58506496;