chr10-100356554-A-G

Variant names:

• chr10-100356554-A-G
• rs2234970
• NM_005063.5:c.670A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005063.5(SCD):​c.670A>G​(p.Met224Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCD NM_005063.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037804455).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCD	NM_005063.5	MANE Select	c.670A>G	p.Met224Val	missense	Exon 5 of 6	NP_005054.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCD	ENST00000370355.3	TSL:1 MANE Select	c.670A>G	p.Met224Val	missense	Exon 5 of 6	ENSP00000359380.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 727120

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111816

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0020
DANN	Benign	0.52
DEOGEN2	Benign	0.22	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.075	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-4.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.021
Sift	Benign	0.076	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.049
MutPred		0.52		Gain of ubiquitination at K219 (P = 0.0804)
MVP		0.24
MPC		0.66
ClinPred		0.085	T
GERP RS		-8.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.50
Mutation Taster		=95/5	polymorphism

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;