6-151536354-C-G

Position:

• chr6-151536354-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025059.4(CCDC170):​c.94C>G​(p.Arg32Gly) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC170 NM_025059.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.315

Genes affected

CCDC170 (HGNC:21177): (coiled-coil domain containing 170) The function of this gene and its encoded protein is not known. Several genome-wide association studies have implicated the region around this gene to be involved in breast cancer and bone mineral density, but no link to this specific gene has been found. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2289964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC170	NM_025059.4	c.94C>G	p.Arg32Gly	missense_variant	2/11	ENST00000239374.8
CCDC170	XM_011536147.3	c.112C>G	p.Arg38Gly	missense_variant	2/11
CCDC170	XM_011536148.3	c.112C>G	p.Arg38Gly	missense_variant	2/10
CCDC170	XM_047419372.1	c.94C>G	p.Arg32Gly	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC170	ENST00000239374.8	c.94C>G	p.Arg32Gly	missense_variant	2/11	1	NM_025059.4	P1
CCDC170	ENST00000544131.1	n.84C>G		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Mar 19, 2024

The c.94C>G (p.R32G) alteration is located in exon 2 (coding exon 2) of the CCDC170 gene. This alteration results from a C to G substitution at nucleotide position 94, causing the arginine (R) at amino acid position 32 to be replaced by a glycine (G). 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	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.065
Eigen_PC	Benign	-0.039
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.97	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.16
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.030	D
Polyphen		0.94	P
Vest4		0.35
MutPred		0.23		Loss of glycosylation at T31 (P = 0.0591);
MVP		0.19
MPC		0.38
ClinPred		0.96	D
GERP RS		4.2
Varity_R		0.14
gMVP		0.30

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: chr6-151857489;