Genetic Variant CCDC175:p.Glu522Lys (chr14-59538082-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.1564G>A(p.Glu522Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,532,346 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CCDC175
NM_001164399.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Publications

0 publications found

Variant links:

Genes affected

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

CCDC175 links:

Genome browser will be placed here

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=0.10030094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC175	NM_001164399.2 link	c.1564G>A	p.Glu522Lys	missense_variant	Exon 13 of 20	ENST00000537690.7	NP_001157871.1	P0C221

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC175	ENST00000537690.7 link	c.1564G>A	p.Glu522Lys	missense_variant	Exon 13 of 20	5	NM_001164399.2	ENSP00000453940.1		P0C221
CCDC175	ENST00000281581.5 link	c.1564G>A	p.Glu522Lys	missense_variant	Exon 13 of 20	5		ENSP00000452964.1		A0A0A0MTQ8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

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:

0.00000217

AC:

AN:

1380216

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

681384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31502

American (AMR)

AF:

0.00

AC:

AN:

35644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25132

East Asian (EAS)

AF:

0.00

AC:

AN:

35590

South Asian (SAS)

AF:

0.00

AC:

AN:

79058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5680

European-Non Finnish (NFE)

AF:

0.00000279

AC:

AN:

1074830

Other (OTH)

AF:

0.00

AC:

AN:

57734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 22, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1564G>A (p.E522K) alteration is located in exon 13 (coding exon 13) of the CCDC175 gene. This alteration results from a G to A substitution at nucleotide position 1564, causing the glutamic acid (E) at amino acid position 522 to be replaced by a lysine (K). 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

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0091

T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

L;.

PhyloP100

1.2

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.5

N;N

Sift

Benign

0.14

T;T

Sift4G

Uncertain

0.059

T;T

Vest4

0.17

MVP

0.030

ClinPred

0.099

GERP RS

3.1

Varity_R

0.067

gMVP

0.18

Mutation Taster

=95/5

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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14-59538082-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