Genetic Variant CCDC175:p.Gly645Arg (chr14-59525344-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164399.2(CCDC175):c.1933G>A(p.Gly645Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000296 in 1,350,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

CCDC175
NM_001164399.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Publications

0 publications found

Variant links:

Genes affected

CCDC175 (HGNC:19847): (coiled-coil domain containing 175)

CCDC175 links:

ENSG00000258782 (HGNC:):

ENSG00000258782 links:

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ACMG classification

Classification was made for transcript

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=0.15788376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC175	NM_001164399.2 link	c.1933G>A	p.Gly645Arg	missense_variant	Exon 16 of 20	ENST00000537690.7	NP_001157871.1	P0C221

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC175	ENST00000537690.7 link	c.1933G>A	p.Gly645Arg	missense_variant	Exon 16 of 20	5	NM_001164399.2	ENSP00000453940.1	P0C221
CCDC175	ENST00000281581.5 link	c.1933G>A	p.Gly645Arg	missense_variant	Exon 16 of 20	5		ENSP00000452964.1	A0A0A0MTQ8
ENSG00000258782	ENST00000554253.1 link	n.94G>A		non_coding_transcript_exon_variant	Exon 1 of 6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000296

AC:

AN:

1350264

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

666382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28764

American (AMR)

AF:

0.00

AC:

AN:

27268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24226

East Asian (EAS)

AF:

0.0000291

AC:

AN:

34308

South Asian (SAS)

AF:

0.00

AC:

AN:

73440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5458

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1065662

Other (OTH)

AF:

0.0000177

AC:

AN:

56528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Jan 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1933G>A (p.G645R) alteration is located in exon 16 (coding exon 16) of the CCDC175 gene. This alteration results from a G to A substitution at nucleotide position 1933, causing the glycine (G) at amino acid position 645 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0062

T;T

Eigen

Benign

-0.015

Eigen_PC

Benign

0.046

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.

PhyloP100

1.1

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.60

N;N

Sift

Benign

0.031

D;D

Sift4G

Benign

0.16

T;T

Vest4

0.20

MVP

0.16

ClinPred

0.38

GERP RS

4.0

Varity_R

0.095

gMVP

0.062

Mutation Taster

=97/3

polymorphism

(source)

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

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14-59525344-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over