chr4-82798420-C-G

Variant names:

• chr4-82798420-C-G
• rs759488147
• NM_001037582.3:c.118G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001037582.3(SCD5):​c.118G>C​(p.Gly40Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,461,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.000011 (0 hom.)
• Consequence: SCD5 NM_001037582.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

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: AD, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.91657 (below the threshold of 3.09). Trascript score misZ: 1.4213 (below the threshold of 3.09). GenCC associations: The gene is linked to hearing loss, autosomal dominant 79.
• BP4: Computational evidence support a benign effect (MetaRNN=0.09243658).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037582.3. 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
	SCD5	NM_001037582.3	MANE Select	c.118G>C	p.Gly40Arg	missense	Exon 1 of 5	NP_001032671.2	Q86SK9-1
	SCD5	NM_024906.3		c.118G>C	p.Gly40Arg	missense	Exon 1 of 4	NP_079182.2	Q86SK9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCD5	ENST00000319540.9	TSL:1 MANE Select	c.118G>C	p.Gly40Arg	missense	Exon 1 of 5	ENSP00000316329.4	Q86SK9-1
	SCD5	ENST00000273908.4	TSL:2	c.118G>C	p.Gly40Arg	missense	Exon 1 of 4	ENSP00000273908.4	Q86SK9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248046 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1461080 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726908

African (AFR) AF: 0.0000598 AC: 2 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111692

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.12
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.032
Sift	Benign	0.43	T
Sift4G	Benign	0.53	T
Polyphen		0.0070	B
Vest4		0.054
MutPred		0.41		Loss of sheet (P = 0.003)
MVP		0.27
MPC		0.39
ClinPred		0.21	T
GERP RS		2.5
PromoterAI		0.042	Neutral
Varity_R		0.057
gMVP		0.35
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs759488147; hg19: chr4-83719573;