10-32451677-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395015.1(CCDC7):c.35A>G(p.Asn12Ser) 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 benign outcome for this variant. 15/21 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: CCDC7 NM_001395015.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.462

Genes affected

CCDC7 (HGNC:26533): (coiled-coil domain containing 7)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041056693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC7	NM_001395015.1	c.35A>G	p.Asn12Ser	missense_variant	2/44	ENST00000639629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC7	ENST00000639629.2	c.35A>G	p.Asn12Ser	missense_variant	2/44	5	NM_001395015.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 08, 2023

The c.35A>G (p.N12S) alteration is located in exon 2 (coding exon 1) of the CCDC7 gene. This alteration results from a A to G substitution at nucleotide position 35, causing the asparagine (N) at amino acid position 12 to be replaced by a serine (S). 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	0.081
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.93
Dann	Benign	0.42
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0089	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.041	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;.;.;.;L
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.35	N;N;N;N;N;.
REVEL	Benign	0.015
Sift	Benign	0.39	T;T;T;T;T;.
Sift4G	Benign	0.77	T;T;T;T;T;.
Polyphen		0.0030	.;.;B;.;.;B
Vest4		0.16
MutPred		0.11		Gain of glycosylation at N12 (P = 0.0325);Gain of glycosylation at N12 (P = 0.0325);Gain of glycosylation at N12 (P = 0.0325);Gain of glycosylation at N12 (P = 0.0325);Gain of glycosylation at N12 (P = 0.0325);Gain of glycosylation at N12 (P = 0.0325);
MVP		0.22
MPC		0.053
ClinPred		0.058	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.0053

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-32740605;