chr4-76328956-G-A

Variant names:

• chr4-76328956-G-A
• rs558880123
• NM_001394954.1:c.2954C>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.2954C>T​(p.Thr985Ile) 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. 15/22 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. T985R) 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: 1.70
• 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=0.12062073).

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.2954C>T	p.Thr985Ile	missense	Exon 22 of 25	NP_001381883.1	A0A804HIY6
	CCDC158	NM_001042784.1		c.2942C>T	p.Thr981Ile	missense	Exon 21 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.2954C>T	p.Thr985Ile	missense	Exon 22 of 25	ENSP00000507278.1	A0A804HIY6
	CCDC158	ENST00000504667.2	TSL:1	n.2820C>T		non_coding_transcript_exon	Exon 10 of 13
	CCDC158	ENST00000388914.7	TSL:5	c.2942C>T	p.Thr981Ile	missense	Exon 21 of 24	ENSP00000373566.2	Q5M9N0-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249446 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.7
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.043
Sift	Benign	0.16	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.16	B
Vest4		0.41
MutPred		0.17		Gain of glycosylation at S976 (P = 0.0075)
MVP		0.46
MPC		0.029
ClinPred		0.20	T
GERP RS		5.1
Varity_R		0.084
gMVP		0.22
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs558880123; hg19: chr4-77250109;