rs61732512

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
• Publications: 1 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 -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 VariationId 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.

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.924C>T	p.Tyr308Tyr	synonymous	Exon 6 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.924C>T	p.Tyr308Tyr	synonymous	Exon 6 of 6	ENSP00000359380.2	O00767
	SCD	ENST00000884321.1		c.1059C>T	p.Tyr353Tyr	synonymous	Exon 6 of 6	ENSP00000554380.1
	SCD	ENST00000884322.1		c.981C>T	p.Tyr327Tyr	synonymous	Exon 7 of 7	ENSP00000554381.1

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

African (AFR) AF: 0.0744 AC: 2490 AN: 33468

American (AMR) AF: 0.00494 AC: 221 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86250

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00451 AC: 26 AN: 5762

European-Non Finnish (NFE) AF: 0.000300 AC: 334 AN: 1111832

Other (OTH) 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

African (AFR) AF: 0.0707 AC: 2937 AN: 41548

American (AMR) AF: 0.0110 AC: 168 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68040

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		0.42
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

Other links and lift over

dbSNP: rs61732512; hg19: chr10-102120534;