4-82636705-T-A

Variant names:

• chr4-82636705-T-A
• rs1727439061
• NM_001037582.3:c.688A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001037582.3(SCD5):​c.688A>T​(p.Ile230Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I230V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCD5 NM_001037582.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• 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 2 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=0.35064608).

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.688A>T	p.Ile230Phe	missense	Exon 4 of 5	NP_001032671.2	Q86SK9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCD5	ENST00000319540.9	TSL:1 MANE Select	c.688A>T	p.Ile230Phe	missense	Exon 4 of 5	ENSP00000316329.4	Q86SK9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.20
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.094	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.49	N
PhyloP100		-1.1
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.077
Sift	Benign	1.0	T
Sift4G	Benign	0.98	T
Polyphen		0.0	B
Vest4		0.66
MutPred		0.68		Gain of sheet (P = 0.0344)
MVP		0.014
MPC		0.52
ClinPred		0.039	T
GERP RS		-3.3
Varity_R		0.045
gMVP		0.70
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1727439061; hg19: chr4-83557858;