10-100360777-C-T

Variant names:

• chr10-100360777-C-T
• rs61732512
• NM_005063.5:c.924C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005063.5(SCD):​c.924C>T​(p.Tyr308Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,613,978 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (108 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (98 hom.)
• Consequence: SCD NM_005063.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.418

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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 10-100360777-C-T is Benign according to our data. Variant chr10-100360777-C-T is described in ClinVar as [Benign]. Clinvar id is 773538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.418 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCD	NM_005063.5	c.924C>T	p.Tyr308Tyr	synonymous_variant	Exon 6 of 6	ENST00000370355.3	NP_005054.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCD	ENST00000370355.3	c.924C>T	p.Tyr308Tyr	synonymous_variant	Exon 6 of 6	1	NM_005063.5	ENSP00000359380.2

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3169 AN: 152204 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00573 AC: 1439 AN: 251130 AF XY: 0.00429

Gnomad AFR exome AF: 0.0749

Gnomad AMR exome AF: 0.00425

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000362

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00235 AC: 3438 AN: 1461656 Hom.: 98 Cov.: 31 AF XY: 0.00212 AC XY: 1539 AN XY: 727142

Gnomad4 AFR exome AF: 0.0744 AC: 2490 AN: 33468

Gnomad4 AMR exome AF: 0.00494 AC: 221 AN: 44716

Gnomad4 ASJ exome AF: 0.0000765 AC: 2 AN: 26132

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000209 AC: 18 AN: 86250

Gnomad4 FIN exome AF: 0.0000374 AC: 2 AN: 53420

Gnomad4 NFE exome AF: 0.000300 AC: 334 AN: 1111832

Gnomad4 Remaining exome AF: 0.00571 AC: 345 AN: 60376

GnomAD4 genome AF: 0.0209 AC: 3178 AN: 152322 Hom.: 108 Cov.: 33 AF XY: 0.0201 AC XY: 1496 AN XY: 74482

Gnomad4 AFR AF: 0.0707 AC: 0.0706893 AN: 0.0706893

Gnomad4 AMR AF: 0.0110 AC: 0.0109718 AN: 0.0109718

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000622 AC: 0.000621633 AN: 0.000621633

Gnomad4 FIN AF: 0.0000941 AC: 0.0000941265 AN: 0.0000941265

Gnomad4 NFE AF: 0.000397 AC: 0.000396825 AN: 0.000396825

Gnomad4 OTH AF: 0.0170 AC: 0.0170293 AN: 0.0170293

Alfa AF: 0.0103 Hom.: 22

Bravo AF: 0.0245

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61732512; hg19: chr10-102120534;