1-162855166-C-A

Variant summary

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

The NM_001394065.1(CCDC190):c.505G>T(p.Asp169Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC190 NM_001394065.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.167

Genes affected

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

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=0.09796849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC190	NM_001394065.1	c.505G>T	p.Asp169Tyr	missense_variant	4/4	ENST00000367912.7
CCDC190	NM_178550.6	c.508G>T	p.Asp170Tyr	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC190	ENST00000367912.7	c.505G>T	p.Asp169Tyr	missense_variant	4/4	5	NM_001394065.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 249198 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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: 0.00000137 AC: 2 AN: 1461686 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

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

Mar 07, 2023

The c.508G>T (p.D170Y) alteration is located in exon 4 (coding exon 3) of the CCDC190 gene. This alteration results from a G to T substitution at nucleotide position 508, causing the aspartic acid (D) at amino acid position 170 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	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	12
Dann	Benign	0.97
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.56	T;T;.
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Pathogenic	-6.1	D;.;D
REVEL	Benign	0.078
Sift	Benign	0.14	T;.;T
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.45	B;B;B
Vest4		0.26
MutPred		0.14		.;Gain of phosphorylation at D170 (P = 0.0478);Gain of phosphorylation at D170 (P = 0.0478);
MVP		0.15
MPC		0.13
ClinPred		0.19	T
GERP RS		2.3
Varity_R		0.098
gMVP		0.14

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: rs755743623; hg19: chr1-162824956;