4-76325985-C-A

Variant names:

• chr4-76325985-C-A
• rs375412402
• NM_001394954.1:c.3041G>T

Variant summary

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

The NM_001394954.1(CCDC158):​c.3041G>T​(p.Arg1014Leu) 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. 14/22 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. R1014H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC158 NM_001394954.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763
• Publications: 3 publications found

Genes affected

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

CCDC158 Gene-Disease associations (from GenCC):

• renal tubule disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3961745).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394954.1. 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
	CCDC158	NM_001394954.1	MANE Select	c.3041G>T	p.Arg1014Leu	missense	Exon 23 of 25	NP_001381883.1	A0A804HIY6
	CCDC158	NM_001042784.1		c.3029G>T	p.Arg1010Leu	missense	Exon 22 of 24	NP_001036249.1	Q5M9N0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC158	ENST00000682701.1	MANE Select	c.3041G>T	p.Arg1014Leu	missense	Exon 23 of 25	ENSP00000507278.1	A0A804HIY6
	CCDC158	ENST00000504667.2	TSL:1	n.2907G>T		non_coding_transcript_exon	Exon 11 of 13
	CCDC158	ENST00000388914.7	TSL:5	c.3029G>T	p.Arg1010Leu	missense	Exon 22 of 24	ENSP00000373566.2	Q5M9N0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0030	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.76
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.14
Sift	Benign	0.048	D
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.42
MutPred		0.22		Gain of glycosylation at S1011 (P = 0.0035)
MVP		0.59
MPC		0.22
ClinPred		0.89	D
GERP RS		4.1
Varity_R		0.061
gMVP		0.31
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs375412402; hg19: chr4-77247138;