NM_005063.5:c.648-543T>C

Variant names:

• chr10-100355989-T-C
• rs3793767
• NM_005063.5:c.648-543T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SCD	NM_005063.5	c.648-543T>C		intron_variant	Intron 4 of 5	ENST00000370355.3	NP_005054.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCD	ENST00000370355.3	c.648-543T>C		intron_variant	Intron 4 of 5	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

African (AFR) AF: 0.346 AC: 14343 AN: 41448

American (AMR) AF: 0.486 AC: 7431 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1960 AN: 5156

South Asian (SAS) AF: 0.293 AC: 1413 AN: 4820

European-Finnish (FIN) AF: 0.371 AC: 3916 AN: 10560

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.413 AC: 28092 AN: 67964

Other (OTH) AF: 0.426 AC: 901 AN: 2116

Alfa AF: 0.406 Hom.: 9150

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
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs3793767; hg19: chr10-102115746;