chr1-162855210-G-A

Position:

• chr1-162855210-G-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.461C>T​(p.Pro154Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,694 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: 0.0000021 (0 hom.)
• Consequence: CCDC190 NM_001394065.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.413

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=0.07543871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC190	NM_001394065.1	c.461C>T	p.Pro154Leu	missense_variant	4/4	ENST00000367912.7
CCDC190	NM_178550.6	c.464C>T	p.Pro155Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC190	ENST00000367912.7	c.461C>T	p.Pro154Leu	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: 0.0000148 AC XY: 2 AN XY: 135190

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000885

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461694 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

Aug 16, 2021

The c.464C>T (p.P155L) alteration is located in exon 4 (coding exon 3) of the CCDC190 gene. This alteration results from a C to T substitution at nucleotide position 464, causing the proline (P) at amino acid position 155 to be replaced by a leucine (L). 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	0.086
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	5.6
DANN	Benign	0.80
DEOGEN2	Benign	0.089	.;T;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.67	T;T;.
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.075	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Pathogenic	-6.6	D;.;D
REVEL	Benign	0.14
Sift	Benign	0.068	T;.;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.010	B;B;B
Vest4		0.20
MutPred		0.11		.;Gain of stability (P = 0.0068);Gain of stability (P = 0.0068);
MVP		0.17
MPC		0.022
ClinPred		0.19	T
GERP RS		2.3
Varity_R		0.11
gMVP		0.068

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: rs1309812946; hg19: chr1-162825000;