Variant 14-59511765-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164399.2(CCDC175):c.2137G>A(p.Val713Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000651 in 1,536,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

CCDC175
NM_001164399.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.25

Variant links:

Genes affected

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

CCDC175 links:

ENSG00000258782 (HGNC:):

ENSG00000258782 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042007715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC175	NM_001164399.2 linkuse as main transcript	c.2137G>A	p.Val713Ile	missense_variant	18/20	ENST00000537690.7	NP_001157871.1	P0C221

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC175	ENST00000537690.7 linkuse as main transcript	c.2137G>A	p.Val713Ile	missense_variant	18/20	5	NM_001164399.2	ENSP00000453940.1	P0C221
CCDC175	ENST00000281581.5 linkuse as main transcript	c.2137G>A	p.Val713Ile	missense_variant	18/20	5		ENSP00000452964.1	A0A0A0MTQ8
ENSG00000258782	ENST00000554253.1 linkuse as main transcript	n.298G>A		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000650

AC:

AN:

1384338

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

683148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000649

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2024

The c.2137G>A (p.V713I) alteration is located in exon 18 (coding exon 18) of the CCDC175 gene. This alteration results from a G to A substitution at nucleotide position 2137, causing the valine (V) at amino acid position 713 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.28

DANN

Benign

0.63

DEOGEN2

Benign

0.0036

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

0.010

N;N

Sift

Benign

0.71

T;T

Sift4G

Benign

0.96

T;T

Vest4

0.076

MVP

0.014

ClinPred

0.021

GERP RS

-3.8

Varity_R

0.024

gMVP

0.037

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