1-162859613-T-C

Variant summary

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

The NM_001394065.1(CCDC190):c.34A>G(p.Lys12Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 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: 3.67

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=0.21403134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC190	NM_001394065.1	c.34A>G	p.Lys12Glu	missense_variant	2/4	ENST00000367912.7
CCDC190	NM_178550.6	c.34A>G	p.Lys12Glu	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC190	ENST00000367912.7	c.34A>G	p.Lys12Glu	missense_variant	2/4	5	NM_001394065.1	A2
CCDC190	ENST00000367910.5	c.34A>G	p.Lys12Glu	missense_variant	2/4	2		P4
CCDC190	ENST00000367911.3	c.34A>G	p.Lys12Glu	missense_variant	1/3	3		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Sep 01, 2021

The c.34A>G (p.K12E) alteration is located in exon 2 (coding exon 1) of the CCDC190 gene. This alteration results from a A to G substitution at nucleotide position 34, causing the lysine (K) at amino acid position 12 to be replaced by a glutamic acid (E). 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	0.26
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	19
Dann	Uncertain	1.0
Eigen	Benign	0.025
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.65	T;T;.
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.80	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Uncertain	-3.2	D;.;D
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D;.;D
Sift4G	Uncertain	0.023	D;D;D
Polyphen		0.93	P;P;P
Vest4		0.43
MutPred		0.30		Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);
MVP		0.12
MPC		0.020
ClinPred		0.85	D
GERP RS		4.5
Varity_R		0.26
gMVP		0.017

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: rs1571045096; hg19: chr1-162829403;