Variant 14-59510684-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001164399.2(CCDC175):c.2267G>A(p.Arg756His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,537,196 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

CCDC175
NM_001164399.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.19

Variant links:

Genes affected

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

CCDC175 links:

CCDC175 (HGNC:):

CCDC175 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043376416).

BP6

Variant 14-59510684-C-T is Benign according to our data. Variant chr14-59510684-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2390763.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC175	NM_001164399.2 linkuse as main transcript	c.2267G>A	p.Arg756His	missense_variant	19/20	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.2267G>A	p.Arg756His	missense_variant	19/20	5	NM_001164399.2	ENSP00000453940.1	P0C221
CCDC175	ENST00000281581.5 linkuse as main transcript	c.2267G>A	p.Arg756His	missense_variant	19/20	5		ENSP00000452964.1	A0A0A0MTQ8
CCDC175	ENST00000553317.1 linkuse as main transcript	n.30G>A		non_coding_transcript_exon_variant	1/3	3
ENSG00000258782	ENST00000554253.1 linkuse as main transcript	n.428G>A		non_coding_transcript_exon_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000898

AC:

AN:

144720

Hom.:

AF XY:

0.0000907

AC XY:

AN XY:

77196

show subpopulations

Gnomad AFR exome

AF:

0.000262

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000941

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000191

AC:

264

AN:

1384912

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

125

AN XY:

683364

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.0000856

Gnomad4 NFE exome

AF:

0.000226

Gnomad4 OTH exome

AF:

0.000155

GnomAD4 genome

AF:

0.000131

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000192

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:

0.000176

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000110

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.023

DANN

Benign

0.60

DEOGEN2

Benign

0.0034

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.11

N;.

PrimateAI

Benign

0.21

PROVEAN

Benign

0.41

N;N

Sift

Benign

0.48

T;T

Sift4G

Benign

0.52

T;T

Vest4

0.036

MVP

0.030

ClinPred

0.020

GERP RS

-4.6

Varity_R

0.017

gMVP

0.080

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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