Genetic Variant SCD5:c.232+25176C>T (chr4-82773130-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001037582.3(SCD5):c.232+25176C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,948 control chromosomes in the GnomAD database, including 20,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 20584 hom., cov: 31)

Consequence

SCD5
NM_001037582.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.153

Publications

11 publications found

Variant links:

Genes affected

SCD5 (HGNC:21088): (stearoyl-CoA desaturase 5) Stearoyl-CoA desaturase (SCD; EC 1.14.99.5) is an integral membrane protein of the endoplasmic reticulum that catalyzes the formation of monounsaturated fatty acids from saturated fatty acids. SCD may be a key regulator of energy metabolism with a role in obesity and dislipidemia. Four SCD isoforms, Scd1 through Scd4, have been identified in mouse. In contrast, only 2 SCD isoforms, SCD1 (MIM 604031) and SCD5, have been identified in human. SCD1 shares about 85% amino acid identity with all 4 mouse SCD isoforms, as well as with rat Scd1 and Scd2. In contrast, SCD5 shares limited homology with the rodent SCDs and appears to be unique to primates (Wang et al., 2005 [PubMed 15907797]).[supplied by OMIM, Mar 2008]

SCD5 Gene-Disease associations (from GenCC):

hearing loss, autosomal dominant 79
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

SCD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCD5	NM_001037582.3 link	c.232+25176C>T		intron_variant	Intron 1 of 4	ENST00000319540.9	NP_001032671.2	Q86SK9-1Q86UC8
SCD5	NM_024906.3 link	c.232+25176C>T		intron_variant	Intron 1 of 3		NP_079182.2	Q86SK9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCD5	ENST00000319540.9 link	c.232+25176C>T		intron_variant	Intron 1 of 4	1	NM_001037582.3	ENSP00000316329.4		Q86SK9-1
SCD5	ENST00000273908.4 link	c.232+25176C>T		intron_variant	Intron 1 of 3	2		ENSP00000273908.4		Q86SK9-2

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71340

AN:

151830

Hom.:

20574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.586

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.509

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.539

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.470

AC:

71364

AN:

151948

Hom.:

20584

Cov.:

AF XY:

0.472

AC XY:

35054

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.130

AC:

5378

AN:

41438

American (AMR)

AF:

0.655

AC:

10006

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.586

AC:

2032

AN:

3470

East Asian (EAS)

AF:

0.262

AC:

1350

AN:

5162

South Asian (SAS)

AF:

0.510

AC:

2447

AN:

4802

European-Finnish (FIN)

AF:

0.589

AC:

6216

AN:

10558

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.620

AC:

42135

AN:

67930

Other (OTH)

AF:

0.541

AC:

1142

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1535

3070

4606

6141

7676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.551

Hom.:

49318

Bravo

AF:

0.460

Asia WGS

AF:

0.405

AC:

1405

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.48

(source)

DANN

Benign

0.63

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over