NM_001395015.1:c.25A>G

Variant names:

• chr10-32451667-A-G
• rs1415534098
• NM_001395015.1:c.25A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001395015.1(CCDC7):​c.25A>G​(p.Thr9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,609,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CCDC7 NM_001395015.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.39
• Publications: 1 publications found

Genes affected

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

CCDC7 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05926454).
• BP6: Variant 10-32451667-A-G is Benign according to our data. Variant chr10-32451667-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2303917.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395015.1. 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
	CCDC7	NM_001395015.1	MANE Select	c.25A>G	p.Thr9Ala	missense	Exon 2 of 44	NP_001381944.1	Q96M83-1
	CCDC7	NM_001321115.2		c.25A>G	p.Thr9Ala	missense	Exon 2 of 44	NP_001308044.1	Q96M83-1
	CCDC7	NM_001395233.1		c.25A>G	p.Thr9Ala	missense	Exon 2 of 15	NP_001382162.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC7	ENST00000639629.2	TSL:5 MANE Select	c.25A>G	p.Thr9Ala	missense	Exon 2 of 44	ENSP00000491655.1	Q96M83-1
	CCDC7	ENST00000277657.12	TSL:1	c.25A>G	p.Thr9Ala	missense	Exon 2 of 18	ENSP00000277657.6	Q96M83-3
	CCDC7	ENST00000362006.11	TSL:1	c.25A>G	p.Thr9Ala	missense	Exon 2 of 18	ENSP00000355078.5	Q96M83-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000121 AC: 3 AN: 248554 AF XY: 0.00000745

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000888

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457772 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724772

African (AFR) AF: 0.00 AC: 0 AN: 33270

American (AMR) AF: 0.0000678 AC: 3 AN: 44246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 85246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110098

Other (OTH) AF: 0.00 AC: 0 AN: 60238

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.11
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.014
DANN	Benign	0.73
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.025	N
PhyloP100		-2.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.034
Sift	Benign	0.25	T
Sift4G	Benign	0.36	T
Polyphen		0.0010	B
Vest4		0.080
MutPred		0.26		Loss of sheet (P = 0.0181)
MVP		0.16
MPC		0.058
ClinPred		0.050	T
GERP RS		-11
PromoterAI		0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.011
Mutation Taster		=99/1	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: rs1415534098; hg19: chr10-32740595;