chr4-76332456-C-A

Variant names:

• chr4-76332456-C-A
• NM_001394954.1:c.2858G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394954.1(CCDC158):​c.2858G>T​(p.Ser953Ile) 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. 16/22 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: 0.446
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.102787286).

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.2858G>T	p.Ser953Ile	missense	Exon 20 of 25	NP_001381883.1	A0A804HIY6
	CCDC158	NM_001042784.1		c.2846G>T	p.Ser949Ile	missense	Exon 19 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.2858G>T	p.Ser953Ile	missense	Exon 20 of 25	ENSP00000507278.1	A0A804HIY6
	CCDC158	ENST00000504667.2	TSL:1	n.2724G>T		non_coding_transcript_exon	Exon 8 of 13
	CCDC158	ENST00000388914.7	TSL:5	c.2846G>T	p.Ser949Ile	missense	Exon 19 of 24	ENSP00000373566.2	Q5M9N0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.45
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.011
Sift	Benign	0.034	D
Sift4G	Benign	0.066	T
Polyphen		0.26	B
Vest4		0.34
MutPred		0.22		Gain of glycosylation at S952 (P = 0.0151)
MVP		0.38
MPC		0.037
ClinPred		0.17	T
GERP RS		2.0
Varity_R		0.080
gMVP		0.28
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr4-77253609;