10-32518437-G-T

Variant summary

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

The NM_001395015.1(CCDC7):c.925G>T(p.Asp309Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,450,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCDC7 NM_001395015.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC7	NM_001395015.1	c.925G>T	p.Asp309Tyr	missense_variant	12/44	ENST00000639629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC7	ENST00000639629.2	c.925G>T	p.Asp309Tyr	missense_variant	12/44	5	NM_001395015.1	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1450732 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 721482

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000451

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jun 29, 2023

The c.925G>T (p.D309Y) alteration is located in exon 12 (coding exon 11) of the CCDC7 gene. This alteration results from a G to T substitution at nucleotide position 925, causing the aspartic acid (D) at amino acid position 309 to be replaced by a tyrosine (Y). 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	Uncertain	0.38
BayesDel_addAF	Benign	0.0071	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	16
Dann	Uncertain	0.99
Eigen	Benign	-0.027
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;L;L
MutationTaster	Benign	0.96	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.7	D;D;.
REVEL	Benign	0.26
Sift	Uncertain	0.0040	D;D;.
Sift4G	Benign	0.075	T;T;.
Polyphen		1.0	.;.;D
Vest4		0.71
MutPred		0.34		Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);
MVP		0.65
MPC		0.38
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.056
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.40		Position offset: -21

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: chr10-32807365;