Genetic Variant CCDC170:p.Glu273Gly (chr6-151573217-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_025059.4(CCDC170):c.818A>G(p.Glu273Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC170
NM_025059.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21

Variant links:

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]

CCDC170 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC170	NM_025059.4 link	c.818A>G	p.Glu273Gly	missense_variant	Exon 6 of 11	ENST00000239374.8	NP_079335.2	Q8IYT3
CCDC170	XM_011536147.3 link	c.836A>G	p.Glu279Gly	missense_variant	Exon 6 of 11		XP_011534449.1
CCDC170	XM_011536148.3 link	c.836A>G	p.Glu279Gly	missense_variant	Exon 6 of 10		XP_011534450.1
CCDC170	XM_047419372.1 link	c.818A>G	p.Glu273Gly	missense_variant	Exon 6 of 10		XP_047275328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC170	ENST00000239374.8 link	c.818A>G	p.Glu273Gly	missense_variant	Exon 6 of 11	1	NM_025059.4	ENSP00000239374.6		Q8IYT3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249294

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.818A>G (p.E273G) alteration is located in exon 6 (coding exon 6) of the CCDC170 gene. This alteration results from a A to G substitution at nucleotide position 818, causing the glutamic acid (E) at amino acid position 273 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

0.25

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.73

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.25

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.71

MutPred

0.28

Loss of stability (P = 0.0104);

MVP

0.34

MPC

0.59

ClinPred

0.98

GERP RS

5.5

Varity_R

0.64

gMVP

0.41

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over