4-140343661-A-C

Position:

• chr4-140343661-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032547.3(SCOC):​c.23A>C​(p.Glu8Ala) 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. 11/15 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)
• Consequence: SCOC NM_032547.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33

Genes affected

SCOC (HGNC:20335): (short coiled-coil protein) This gene encodes a short coiled-coiled domain-containing protein that localizes to the Golgi apparatus. The encoded protein interacts with ADP-ribosylation factor-like proteins. Pseudogenes of this gene are found on chromosomes 1 and 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

SCOC-AS1 (HGNC:):

ACMG classification

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=0.14161885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCOC	NM_001153446.1	c.23A>C	p.Glu8Ala	missense_variant	2/5		NP_001146918.1
SCOC	NM_001153585.1	c.23A>C	p.Glu8Ala	missense_variant	1/4		NP_001147057.1
SCOC	NM_032547.3	c.23A>C	p.Glu8Ala	missense_variant	2/5		NP_115936.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCOC	ENST00000338517.8	c.23A>C	p.Glu8Ala	missense_variant	2/5	4		ENSP00000345262.4
SCOC	ENST00000394203.7	c.23A>C	p.Glu8Ala	missense_variant	1/4	2		ENSP00000377753.3
SCOC	ENST00000394205.7	c.23A>C	p.Glu8Ala	missense_variant	2/5	2		ENSP00000377755.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.23A>C (p.E8A) alteration is located in exon 1 (coding exon 1) of the SCOC gene. This alteration results from a A to C substitution at nucleotide position 23, causing the glutamic acid (E) at amino acid position 8 to be replaced by an alanine (A). 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
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Uncertain	0.99
Eigen	Benign	0.022
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.53	.;.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.67	N;N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.20	T;T;T
Polyphen		0.56	P;P;P
Vest4		0.40
MutPred		0.12		Gain of glycosylation at S4 (P = 0.0102);Gain of glycosylation at S4 (P = 0.0102);Gain of glycosylation at S4 (P = 0.0102);
MVP		0.12
ClinPred		0.55	D
GERP RS		3.8

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-141264815;