Genetic Variant CCDC190:p.Asp169Tyr (chr1-162855166-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394065.1(CCDC190):c.505G>T(p.Asp169Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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: 0.0000014 ( 0 hom. )

Consequence

CCDC190
NM_001394065.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.167

Variant links:

Genes affected

CCDC190 (HGNC:28736): (coiled-coil domain containing 190)

CCDC190 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09796849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC190	NM_001394065.1 link	c.505G>T	p.Asp169Tyr	missense_variant	Exon 4 of 4	ENST00000367912.7	NP_001380994.1
CCDC190	NM_178550.6 link	c.508G>T	p.Asp170Tyr	missense_variant	Exon 4 of 4		NP_848645.3	Q86UF4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC190	ENST00000367912.7 link	c.505G>T	p.Asp169Tyr	missense_variant	Exon 4 of 4	5	NM_001394065.1	ENSP00000356888.3		A0A8J8YXK0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249198

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000137

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.508G>T (p.D170Y) alteration is located in exon 4 (coding exon 3) of the CCDC190 gene. This alteration results from a G to T substitution at nucleotide position 508, causing the aspartic acid (D) at amino acid position 170 to be replaced by a tyrosine (Y). 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

.;T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.56

T;T;.

M_CAP

Benign

0.0045

MetaRNN

Benign

0.098

T;T;T

MetaSVM

Benign

-1.1

PROVEAN

Pathogenic

-6.1

D;.;D

REVEL

Benign

0.078

Sift

Benign

0.14

T;.;T

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.45

B;B;B

Vest4

0.26

MutPred

0.14

.;Gain of phosphorylation at D170 (P = 0.0478);Gain of phosphorylation at D170 (P = 0.0478);

MVP

0.15

MPC

0.13

ClinPred

0.19

GERP RS

2.3

Varity_R

0.098

gMVP

0.14

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

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