1-162859552-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001394065.1(CCDC190):c.95T>C(p.Leu32Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 2.81

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC190	NM_001394065.1	c.95T>C	p.Leu32Pro	missense_variant	2/4	ENST00000367912.7
CCDC190	NM_178550.6	c.95T>C	p.Leu32Pro	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC190	ENST00000367912.7	c.95T>C	p.Leu32Pro	missense_variant	2/4	5	NM_001394065.1	A2
CCDC190	ENST00000367910.5	c.95T>C	p.Leu32Pro	missense_variant	2/4	2		P4
CCDC190	ENST00000367911.3	c.95T>C	p.Leu32Pro	missense_variant	1/3	3		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 09, 2023

The c.95T>C (p.L32P) alteration is located in exon 2 (coding exon 1) of the CCDC190 gene. This alteration results from a T to C substitution at nucleotide position 95, causing the leucine (L) at amino acid position 32 to be replaced by a proline (P). 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	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.64	T;T;.
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Benign	-0.45	T
MutationTaster	Benign	0.99	D;D;D
PROVEAN	Pathogenic	-6.5	D;.;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.85
MutPred		0.49		Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP		0.32
MPC		0.10
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.91
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-162829342;