NM_001395015.1:c.67A>C

Variant names:

• chr10-32451709-A-C
• rs1312384322
• NM_001395015.1:c.67A>C

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.67A>C​(p.Lys23Gln) 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 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC7 NM_001395015.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37
• 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=0.2420192).

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.67A>C	p.Lys23Gln	missense	Exon 2 of 44	NP_001381944.1	Q96M83-1
	CCDC7	NM_001321115.2		c.67A>C	p.Lys23Gln	missense	Exon 2 of 44	NP_001308044.1	Q96M83-1
	CCDC7	NM_001395233.1		c.67A>C	p.Lys23Gln	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.67A>C	p.Lys23Gln	missense	Exon 2 of 44	ENSP00000491655.1	Q96M83-1
	CCDC7	ENST00000277657.12	TSL:1	c.67A>C	p.Lys23Gln	missense	Exon 2 of 18	ENSP00000277657.6	Q96M83-3
	CCDC7	ENST00000362006.11	TSL:1	c.67A>C	p.Lys23Gln	missense	Exon 2 of 18	ENSP00000355078.5	Q96M83-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00000398 AC: 1 AN: 250986 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461408 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726960

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111816

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

African (AFR) AF: 0.0000724 AC: 3 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

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	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.016
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.27	T
Polyphen		0.98	D
Vest4		0.27
MutPred		0.33		Loss of methylation at K23 (P = 0.0089)
MVP		0.74
MPC		0.093
ClinPred		0.29	T
GERP RS		5.3
PromoterAI		-0.0040	Neutral
Varity_R		0.058
gMVP		0.042
Mutation Taster		=97/3	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: rs1312384322; hg19: chr10-32740637;