Variant 4-82798492-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037582.3(SCD5):c.46G>T(p.Ala16Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SCD5
NM_001037582.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14353892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCD5	NM_001037582.3 linkuse as main transcript	c.46G>T	p.Ala16Ser	missense_variant	1/5	ENST00000319540.9	NP_001032671.2	Q86SK9-1Q86UC8
SCD5	NM_024906.3 linkuse as main transcript	c.46G>T	p.Ala16Ser	missense_variant	1/4		NP_079182.2	Q86SK9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCD5	ENST00000319540.9 linkuse as main transcript	c.46G>T	p.Ala16Ser	missense_variant	1/5	1	NM_001037582.3	ENSP00000316329.4		Q86SK9-1
SCD5	ENST00000273908.4 linkuse as main transcript	c.46G>T	p.Ala16Ser	missense_variant	1/4	2		ENSP00000273908.4		Q86SK9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725694

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.46G>T (p.A16S) alteration is located in exon 1 (coding exon 1) of the SCD5 gene. This alteration results from a G to T substitution at nucleotide position 46, causing the alanine (A) at amino acid position 16 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.059

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.52

T;T

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.085

Sift

Benign

0.77

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.17

B;P

Vest4

0.15

MutPred

0.31

Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);

MVP

0.17

MPC

0.34

ClinPred

0.66

GERP RS

3.0

Varity_R

0.084

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over