chr1-162859531-C-G

Position:

• chr1-162859531-C-G

Variant summary

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

The NM_001394065.1(CCDC190):​c.116G>C​(p.Cys39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/18 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)
• Consequence: CCDC190 NM_001394065.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

Genes affected

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

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	UniProt
CCDC190	NM_001394065.1	c.116G>C	p.Cys39Ser	missense_variant	2/4	ENST00000367912.7
CCDC190	NM_178550.6	c.116G>C	p.Cys39Ser	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC190	ENST00000367912.7	c.116G>C	p.Cys39Ser	missense_variant	2/4	5	NM_001394065.1	A2
CCDC190	ENST00000367910.5	c.116G>C	p.Cys39Ser	missense_variant	2/4	2		P4
CCDC190	ENST00000367911.3	c.116G>C	p.Cys39Ser	missense_variant	1/3	3		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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 14, 2021

The c.116G>C (p.C39S) alteration is located in exon 2 (coding exon 1) of the CCDC190 gene. This alteration results from a G to C substitution at nucleotide position 116, causing the cysteine (C) at amino acid position 39 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	0.26
BayesDel_addAF	Benign	-0.0066	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.75
Eigen	Benign	0.0071
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.66	T;T;.
M_CAP	Benign	0.0064	T
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Pathogenic	-6.7	D;.;D
REVEL	Benign	0.15
Sift	Benign	0.032	D;.;D
Sift4G	Uncertain	0.033	D;D;D
Polyphen		0.90	P;P;P
Vest4		0.56
MutPred		0.54		Loss of catalytic residue at L40 (P = 0.0238);Loss of catalytic residue at L40 (P = 0.0238);Loss of catalytic residue at L40 (P = 0.0238);
MVP		0.11
MPC		0.023
ClinPred		0.94	D
GERP RS		3.5
Varity_R		0.41
gMVP		0.020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1650424798; hg19: chr1-162829321;