1-162855273-A-C

Variant names:

• chr1-162855273-A-C
• rs777920824
• NM_001394065.1:c.398T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394065.1(CCDC190):​c.398T>G​(p.Met133Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,658 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M133I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CCDC190 NM_001394065.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.71
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05183181).

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.398T>G	p.Met133Arg	missense	Exon 4 of 4	NP_001380994.1	A0A8J8YXK0
	CCDC190	NM_178550.6		c.401T>G	p.Met134Arg	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.398T>G	p.Met133Arg	missense	Exon 4 of 4	ENSP00000356888.3	A0A8J8YXK0
	CCDC190	ENST00000524691.1	TSL:1	n.152+359T>G		intron	N/A
	CCDC190	ENST00000367910.5	TSL:2	c.401T>G	p.Met134Arg	missense	Exon 4 of 4	ENSP00000356886.1	Q86UF4-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248698 AF XY: 0.0000296

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461584 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 727084

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

American (AMR) AF: 0.000112 AC: 5 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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111846

Other (OTH) AF: 0.0000663 AC: 4 AN: 60372

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152074 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74276

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.000458 AC: 7 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.00000828 AC: 1

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	0.088
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.0010
DANN	Benign	0.24
DEOGEN2	Benign	0.074	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.7
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.095
Sift	Benign	0.034	D
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.16		Gain of solvent accessibility (P = 0.0021)
MVP		0.030
MPC		0.027
ClinPred		0.068	T
GERP RS		-8.4
Varity_R		0.45
gMVP		0.14
Mutation Taster		=98/2	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: rs777920824; hg19: chr1-162825063;