chr3-113978238-C-T

Position:

• chr3-113978238-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020817.2(CCDC191):​c.2554G>A​(p.Val852Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.000010 (0 hom.)
• Consequence: CCDC191 NM_020817.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11

Genes affected

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

ZDHHC23 (HGNC:):

ACMG classification

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=0.10062334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC191	NM_020817.2	c.2554G>A	p.Val852Met	missense_variant	16/17	ENST00000295878.8	NP_065868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC191	ENST00000295878.8	c.2554G>A	p.Val852Met	missense_variant	16/17	1	NM_020817.2	ENSP00000295878	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000359 AC: 9 AN: 250940 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135594

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000490

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: 0.0000103 AC: 15 AN: 1461756 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.2554G>A (p.V852M) alteration is located in exon 16 (coding exon 16) of the CCDC191 gene. This alteration results from a G to A substitution at nucleotide position 2554, causing the valine (V) at amino acid position 852 to be replaced by a methionine (M). 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	-0.49	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.068
Sift	Benign	0.044	D
Sift4G	Benign	0.13	T
Polyphen		0.92	P
Vest4		0.14
MutPred		0.28		Loss of sheet (P = 0.0054);
MVP		0.17
MPC		0.21
ClinPred		0.12	T
GERP RS		2.9
Varity_R		0.043
gMVP		0.047

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

Other links and lift over

dbSNP: rs1192166059; hg19: chr3-113697085;