3-113978955-A-G

Position:

• chr3-113978955-A-G

Variant summary

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

The NM_020817.2(CCDC191):​c.2363T>C​(p.Phe788Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: CCDC191 NM_020817.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

Genes affected

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

ZDHHC23 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC191	NM_020817.2	c.2363T>C	p.Phe788Ser	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	c.2363T>C	p.Phe788Ser	missense_variant	15/17	1	NM_020817.2	ENSP00000295878	P1
CCDC191	ENST00000527855.1	n.377T>C		non_coding_transcript_exon_variant	3/3	3
CCDC191	ENST00000460813.5	c.*2432T>C		3_prime_UTR_variant, NMD_transcript_variant	15/16	2		ENSP00000418382

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

Gnomad4 AFR AF: 0.0000483

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: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

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

Jul 11, 2023

The c.2363T>C (p.F788S) alteration is located in exon 15 (coding exon 15) of the CCDC191 gene. This alteration results from a T to C substitution at nucleotide position 2363, causing the phenylalanine (F) at amino acid position 788 to be replaced by a serine (S). 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	0.24
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.13
Sift	Benign	0.26	T
Sift4G	Benign	0.36	T
Polyphen		0.87	P
Vest4		0.62
MutPred		0.56		Gain of disorder (P = 0.0039);
MVP		0.28
MPC		0.71
ClinPred		0.38	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.18

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: rs1248130616; hg19: chr3-113697802;