4-76351055-C-T

Position:

• chr4-76351055-C-T

Variant summary

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

The NM_001394954.1(CCDC158):​c.2605G>A​(p.Val869Ile) 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. 15/21 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)
• Consequence: CCDC158 NM_001394954.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.332

Genes affected

CCDC158 (HGNC:26374): (coiled-coil domain containing 158)

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=0.04908383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC158	NM_001394954.1	c.2605G>A	p.Val869Ile	missense_variant	18/25	ENST00000682701.1	NP_001381883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC158	ENST00000682701.1	c.2605G>A	p.Val869Ile	missense_variant	18/25		NM_001394954.1	ENSP00000507278	A1
CCDC158	ENST00000504667.2	n.2426G>A		non_coding_transcript_exon_variant	6/13	1
CCDC158	ENST00000388914.7	c.2605G>A	p.Val869Ile	missense_variant	17/24	5		ENSP00000373566	P4

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

Jan 03, 2024

The c.2605G>A (p.V869I) alteration is located in exon 17 (coding exon 16) of the CCDC158 gene. This alteration results from a G to A substitution at nucleotide position 2605, causing the valine (V) at amino acid position 869 to be replaced by an isoleucine (I). 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	0.073
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.00074	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.10
Sift	Benign	0.35	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.060
MutPred		0.052		Gain of glycosylation at S868 (P = 0.0492);
MVP		0.57
MPC		0.024
ClinPred		0.072	T
GERP RS		3.5
Varity_R		0.042
gMVP		0.13

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: chr4-77272208;