10-32451666-G-T

Variant names:

• chr10-32451666-G-T
• rs1357439808
• NM_001395015.1:c.24G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395015.1(CCDC7):​c.24G>T​(p.Leu8Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,608,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CCDC7 NM_001395015.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.801
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069276124).

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.24G>T	p.Leu8Phe	missense	Exon 2 of 44	NP_001381944.1	Q96M83-1
	CCDC7	NM_001321115.2		c.24G>T	p.Leu8Phe	missense	Exon 2 of 44	NP_001308044.1	Q96M83-1
	CCDC7	NM_001395233.1		c.24G>T	p.Leu8Phe	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.24G>T	p.Leu8Phe	missense	Exon 2 of 44	ENSP00000491655.1	Q96M83-1
	CCDC7	ENST00000277657.12	TSL:1	c.24G>T	p.Leu8Phe	missense	Exon 2 of 18	ENSP00000277657.6	Q96M83-3
	CCDC7	ENST00000362006.11	TSL:1	c.24G>T	p.Leu8Phe	missense	Exon 2 of 18	ENSP00000355078.5	Q96M83-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152018 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 248216 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000890

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: 0.00000275 AC: 4 AN: 1456812 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 724300

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33260

American (AMR) AF: 0.0000679 AC: 3 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109624

Other (OTH) AF: 0.00 AC: 0 AN: 60198

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0261725), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152018 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74252

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.18
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.80
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.037
Sift	Benign	0.14	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.34		Gain of methylation at K5 (P = 0.0818)
MVP		0.16
MPC		0.29
ClinPred		0.057	T
GERP RS		-9.4
PromoterAI		0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.0041
Mutation Taster		=100/0	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: rs1357439808; hg19: chr10-32740594;