4-140373714-G-A

Position:

• chr4-140373714-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001153663.1(SCOC):​c.178G>A​(p.Glu60Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,394,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SCOC NM_001153663.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.768

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044204086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCOC	NM_001153484.2	c.-54G>A		5_prime_UTR_variant	1/4	ENST00000608372.6	NP_001146956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCOC	ENST00000608372	c.-54G>A		5_prime_UTR_variant	1/4	1	NM_001153484.2	ENSP00000477352.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1394818 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688072

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 21, 2024

The c.178G>A (p.E60K) alteration is located in exon 1 (coding exon 1) of the SCOC gene. This alteration results from a G to A substitution at nucleotide position 178, causing the glutamic acid (E) at amino acid position 60 to be replaced by a lysine (K). 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	0.066
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.010	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.59	T;.;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N;N
PROVEAN	Benign	-0.99	.;.;N
REVEL	Benign	0.047
Sift	Benign	0.31	.;.;T
Sift4G	Benign	0.81	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.024
MutPred		0.23		Gain of ubiquitination at E60 (P = 0.0051);Gain of ubiquitination at E60 (P = 0.0051);Gain of ubiquitination at E60 (P = 0.0051);
MVP		0.014
MPC		0.45
ClinPred		0.10	T
GERP RS		1.5
Varity_R		0.052
gMVP		0.088

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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

Other links and lift over

dbSNP: rs1370434347; hg19: chr4-141294868;