1-162855210-G-A

Variant names:

• chr1-162855210-G-A
• rs1309812946
• NM_001394065.1:c.461C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/19 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07543871).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394065.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC190	NM_001394065.1	MANE Select	c.461C>T	p.Pro154Leu	missense	Exon 4 of 4	NP_001380994.1	A0A8J8YXK0
	CCDC190	NM_178550.6		c.464C>T	p.Pro155Leu	missense	Exon 4 of 4	NP_848645.3	Q86UF4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC190	ENST00000367912.7	TSL:5 MANE Select	c.461C>T	p.Pro154Leu	missense	Exon 4 of 4	ENSP00000356888.3	A0A8J8YXK0
	CCDC190	ENST00000524691.1	TSL:1	n.152+422C>T		intron	N/A
	CCDC190	ENST00000367910.5	TSL:2	c.464C>T	p.Pro155Leu	missense	Exon 4 of 4	ENSP00000356886.1	Q86UF4-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249198 AF XY: 0.0000148

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111858

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.41
PROVEAN	Pathogenic	-6.6	D
REVEL	Benign	0.14
Sift	Benign	0.068	T
Sift4G	Benign	0.11	T
Polyphen		0.010	B
Vest4		0.20
MutPred		0.11		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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1309812946; hg19: chr1-162825000;