rs2234970

chr10-100356554-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2 BP4_Strong BA1

The NM_005063.5(SCD):c.670A>C(p.Met224Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,613,390 control chromosomes in the GnomAD database, including 138,873 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.40 (12454 hom., cov: 32)
  • Exomes 𝑓: 0.41 (126419 hom.)
• Consequence: SCD NM_005063.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97

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 -11 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SCD
• BP4: Computational evidence support a benign effect (MetaRNN=7.6000815E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCD	NM_005063.5	c.670A>C	p.Met224Leu	missense_variant	5/6	ENST00000370355.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCD	ENST00000370355.3	c.670A>C	p.Met224Leu	missense_variant	5/6	1	NM_005063.5	P1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61124 AN: 151922 Hom.: 12443 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.435

GnomAD3 exomes AF: 0.412 AC: 103405 AN: 251106 Hom.: 22140 AF XY: 0.401 AC XY: 54463 AN XY: 135700

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.432

Gnomad EAS exome AF: 0.396

Gnomad SAS exome AF: 0.285

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.413

Gnomad OTH exome AF: 0.413

GnomAD4 exome AF: 0.413 AC: 602809 AN: 1461350 Hom.: 126419 Cov.: 43 AF XY: 0.408 AC XY: 296939 AN XY: 727012

Gnomad4 AFR exome AF: 0.359

Gnomad4 AMR exome AF: 0.558

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.402 AC: 61167 AN: 152040 Hom.: 12454 Cov.: 32 AF XY: 0.398 AC XY: 29569 AN XY: 74308

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.435

Alfa AF: 0.414 Hom.: 33928

Bravo AF: 0.415

TwinsUK AF: 0.405 AC: 1501

ALSPAC AF: 0.411 AC: 1583

ESP6500AA AF: 0.356 AC: 1570

ESP6500EA AF: 0.422 AC: 3627

ExAC AF: 0.403 AC: 48971

Asia WGS AF: 0.342 AC: 1190 AN: 3478

EpiCase AF: 0.419

EpiControl AF: 0.418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.0010
Dann	Benign	0.45
DEOGEN2	Benign	0.21	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.016	T
MetaRNN	Benign	0.0000076	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-3.2	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.059
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.052
MutPred		0.29		Loss of methylation at K219 (P = 0.0771);
MPC		0.61
ClinPred		0.015	T
GERP RS		-8.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.45

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: rs2234970; hg19: chr10-102116311; COSMIC: COSV64852974;