NM_005063.5:c.670A>C

Variant names:

• chr10-100356554-A-C
• rs2234970
• NM_005063.5:c.670A>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.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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. M224V) has been classified as Uncertain significance.

• 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
• Publications: 50 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]

SCD Gene-Disease associations (from GenCC):

• adrenoleukodystrophy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005063.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCD	NM_005063.5	MANE Select	c.670A>C	p.Met224Leu	missense	Exon 5 of 6	NP_005054.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCD	ENST00000370355.3	TSL:1 MANE Select	c.670A>C	p.Met224Leu	missense	Exon 5 of 6	ENSP00000359380.2	O00767
	SCD	ENST00000884321.1		c.805A>C	p.Met269Leu	missense	Exon 5 of 6	ENSP00000554380.1
	SCD	ENST00000884322.1		c.727A>C	p.Met243Leu	missense	Exon 6 of 7	ENSP00000554381.1

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

GnomAD2 exomes AF: 0.412 AC: 103405 AN: 251106 AF XY: 0.401

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 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

African (AFR) AF: 0.359 AC: 12016 AN: 33462

American (AMR) AF: 0.558 AC: 24951 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 11502 AN: 26124

East Asian (EAS) AF: 0.389 AC: 15427 AN: 39694

South Asian (SAS) AF: 0.289 AC: 24957 AN: 86246

European-Finnish (FIN) AF: 0.384 AC: 20522 AN: 53414

Middle Eastern (MID) AF: 0.441 AC: 2542 AN: 5762

European-Non Finnish (NFE) AF: 0.419 AC: 465791 AN: 1111570

Other (OTH) AF: 0.416 AC: 25101 AN: 60372

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

African (AFR) AF: 0.367 AC: 15205 AN: 41470

American (AMR) AF: 0.491 AC: 7499 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1962 AN: 5174

South Asian (SAS) AF: 0.294 AC: 1416 AN: 4816

European-Finnish (FIN) AF: 0.380 AC: 4012 AN: 10560

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28150 AN: 67956

Other (OTH) AF: 0.435 AC: 920 AN: 2114

Alfa AF: 0.412 Hom.: 51195

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 v4.9

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
PhyloP100		-4.0
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
Mutation Taster		=93/7	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: rs2234970; hg19: chr10-102116311; COSMIC: COSV64852974;