Variant 3-113978998-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020817.2(CCDC191):c.2320C>T(p.His774Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000055 ( 0 hom. )

Consequence

CCDC191
NM_020817.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.27

Variant links:

Genes affected

CCDC191 (HGNC:29272): (coiled-coil domain containing 191)

CCDC191 links:

ZDHHC23 (HGNC:):

ZDHHC23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26634115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC191	NM_020817.2 linkuse as main transcript	c.2320C>T	p.His774Tyr	missense_variant	15/17	ENST00000295878.8	NP_065868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC191	ENST00000295878.8 linkuse as main transcript	c.2320C>T	p.His774Tyr	missense_variant	15/17	1	NM_020817.2	ENSP00000295878	P1	Q8NCU4-1
CCDC191	ENST00000527855.1 linkuse as main transcript	n.334C>T		non_coding_transcript_exon_variant	3/3	3
CCDC191	ENST00000460813.5 linkuse as main transcript	c.*2389C>T		3_prime_UTR_variant, NMD_transcript_variant	15/16	2		ENSP00000418382

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

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:

0.00000547

AC:

AN:

1461238

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

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

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2024

The c.2320C>T (p.H774Y) alteration is located in exon 15 (coding exon 15) of the CCDC191 gene. This alteration results from a C to T substitution at nucleotide position 2320, causing the histidine (H) at amino acid position 774 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

0.14

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.67

M_CAP

Benign

0.015

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.15

Sift

Benign

0.076

Sift4G

Benign

0.076

Polyphen

0.087

Vest4

0.54

MutPred

0.40

Gain of glycosylation at Y775 (P = 0.0297);

MVP

0.15

MPC

0.34

ClinPred

0.95

GERP RS

4.3

Varity_R

0.29

gMVP

0.42

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