10-100355989-T-C

Position:

• chr10-100355989-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005063.5(SCD):​c.648-543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,022 control chromosomes in the GnomAD database, including 12,022 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 0.39 (12022 hom., cov: 32)
• Consequence: SCD NM_005063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

Genes affected

SCD (HGNC:10571): (stearoyl-CoA desaturase) This gene encodes an enzyme involved in fatty acid biosynthesis, primarily the synthesis of oleic acid. The protein belongs to the fatty acid desaturase family and is an integral membrane protein located in the endoplasmic reticulum. Transcripts of approximately 3.9 and 5.2 kb, differing only by alternative polyadenlyation signals, have been detected. A gene encoding a similar enzyme is located on chromosome 4 and a pseudogene of this gene is located on chromosome 17. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCD	NM_005063.5	c.648-543T>C		intron_variant		ENST00000370355.3	NP_005054.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCD	ENST00000370355.3	c.648-543T>C		intron_variant		1	NM_005063.5	ENSP00000359380.2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59988 AN: 151904 Hom.: 12012 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.395 AC: 60028 AN: 152022 Hom.: 12022 Cov.: 32 AF XY: 0.390 AC XY: 29007 AN XY: 74288

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.426

Alfa AF: 0.403 Hom.: 6559

Bravo AF: 0.407

Asia WGS AF: 0.344 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.070
DANN	Benign	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

Other links and lift over

dbSNP: rs3793767; hg19: chr10-102115746;