dbSNP rs2234970: SCD:p.Met224Leu (chr10-100356554-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.40 ( 12454 hom., cov: 32)

Exomes 𝑓: 0.41 ( 126419 hom. )

Consequence

SCD
NM_005063.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.97

Variant links:

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]

SCD links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

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 rank	MANE	Protein	UniProt
SCD	NM_005063.5 link	c.670A>C	p.Met224Leu	missense_variant	Exon 5 of 6	ENST00000370355.3	NP_005054.3	O00767

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCD	ENST00000370355.3 link	c.670A>C	p.Met224Leu	missense_variant	Exon 5 of 6	1	NM_005063.5	ENSP00000359380.2		O00767

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61124

AN:

151922

Hom.:

12443

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.408

AC XY:

296939

AN XY:

727012

show subpopulations

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.:

AF XY:

0.398

AC XY:

29569

AN XY:

74308

show subpopulations

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

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.0010

DANN

Benign

0.45

DEOGEN2

Benign

0.21

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.016

MetaRNN

Benign

0.0000076

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-3.2

PrimateAI

Benign

0.39

PROVEAN

Benign

1.3

REVEL

Benign

0.059

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.052

MutPred

0.29

Loss of methylation at K219 (P = 0.0771);

MPC

0.61

ClinPred

0.015

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over