4-76334025-G-T

Position:

• chr4-76334025-G-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.2807C>A​(p.Ala936Asp) 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: 0.00600

Genes affected

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

CCDC158 (HGNC:):

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=0.037391216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC158	NM_001394954.1	c.2807C>A	p.Ala936Asp	missense_variant	19/25	ENST00000682701.1	NP_001381883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC158	ENST00000682701.1	c.2807C>A	p.Ala936Asp	missense_variant	19/25		NM_001394954.1	ENSP00000507278.1
CCDC158	ENST00000504667.2	n.2628C>A		non_coding_transcript_exon_variant	7/13	1
CCDC158	ENST00000388914.7	c.2807C>A	p.Ala936Asp	missense_variant	18/24	5		ENSP00000373566.2

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

Jun 10, 2024

The c.2807C>A (p.A936D) alteration is located in exon 18 (coding exon 17) of the CCDC158 gene. This alteration results from a C to A substitution at nucleotide position 2807, causing the alanine (A) at amino acid position 936 to be replaced by an aspartic acid (D). 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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.6
DANN	Benign	0.79
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.019
Sift	Benign	0.16	T
Sift4G	Uncertain	0.039	D
Polyphen		0.018	B
Vest4		0.19
MutPred		0.17		Gain of glycosylation at S933 (P = 0.0072);
MVP		0.17
MPC		0.036
ClinPred		0.039	T
GERP RS		-2.1
Varity_R		0.074
gMVP		0.25

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: chr4-77255178;