1-162855016-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394065.1(CCDC190):c.655G>A(p.Gly219Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 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: 0.875

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039737433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC190	NM_001394065.1	c.655G>A	p.Gly219Arg	missense_variant	4/4	ENST00000367912.7
CCDC190	NM_178550.6	c.658G>A	p.Gly220Arg	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC190	ENST00000367912.7	c.655G>A	p.Gly219Arg	missense_variant	4/4	5	NM_001394065.1	A2
CCDC190	ENST00000524691.1	n.152+616G>A		intron_variant, non_coding_transcript_variant		1
CCDC190	ENST00000367910.5	c.658G>A	p.Gly220Arg	missense_variant	4/4	2		P4
CCDC190	ENST00000367911.3	c.658G>A	p.Gly220Arg	missense_variant	3/3	3		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Dec 16, 2022

The c.658G>A (p.G220R) alteration is located in exon 4 (coding exon 3) of the CCDC190 gene. This alteration results from a G to A substitution at nucleotide position 658, causing the glycine (G) at amino acid position 220 to be replaced by an arginine (R). 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	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	6.2
Dann	Benign	0.59
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.36	T;.
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
Sift4G	Benign	0.82	T;T
Polyphen		0.0020	B;B
Vest4		0.071
MutPred		0.13		Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);
MVP		0.10
MPC		0.020
ClinPred		0.099	T
GERP RS		-4.9
Varity_R		0.037
gMVP		0.039

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-162824806;