10-100348179-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_005063.5(SCD):c.143C>G(p.Pro48Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,613,918 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (4 hom.)
• Consequence: SCD NM_005063.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.30

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 -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SCD
• BP4: Computational evidence support a benign effect (MetaRNN=0.0060331523).
• BP6: Variant 10-100348179-C-G is Benign according to our data. Variant chr10-100348179-C-G is described in ClinVar as [Benign]. Clinvar id is 731905.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 214 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCD	NM_005063.5	c.143C>G	p.Pro48Arg	missense_variant	2/6	ENST00000370355.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCD	ENST00000370355.3	c.143C>G	p.Pro48Arg	missense_variant	2/6	1	NM_005063.5	P1

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 214 AN: 152016 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.000481

GnomAD3 exomes AF: 0.00150 AC: 376 AN: 251452 Hom.: 1 AF XY: 0.00151 AC XY: 205 AN XY: 135898

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00938

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00132 AC: 1927 AN: 1461784 Hom.: 4 Cov.: 32 AF XY: 0.00130 AC XY: 946 AN XY: 727202

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00951

Gnomad4 NFE exome AF: 0.00122

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.00141 AC: 214 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.00167 AC XY: 124 AN XY: 74376

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0110

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.000476

Alfa AF: 0.00136 Hom.: 1

Bravo AF: 0.000487

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.00147 AC: 179

EpiCase AF: 0.000600

EpiControl AF: 0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	20
Dann	Benign	0.97
DEOGEN2	Uncertain	0.62	D
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.085
Sift	Benign	0.054	T
Sift4G	Uncertain	0.046	D
Polyphen		0.0020	B
Vest4		0.43
MVP		0.33
MPC		1.7
ClinPred		0.058	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.090
gMVP		0.67

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: rs150416868; hg19: chr10-102107936;