Genetic Variant CCDC7:p.Ser137Leu (chr10-32456288-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001395015.1(CCDC7):c.410C>T(p.Ser137Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000338 in 1,566,334 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: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

CCDC7
NM_001395015.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Variant links:

Genes affected

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

CCDC7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CCDC7	NM_001395015.1 link	c.410C>T	p.Ser137Leu	missense_variant	Exon 4 of 44	ENST00000639629.2	NP_001381944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC7	ENST00000639629.2 link	c.410C>T	p.Ser137Leu	missense_variant	Exon 4 of 44	5	NM_001395015.1	ENSP00000491655.1		Q96M83-1

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000362

AC:

AN:

248948

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134580

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000276

AC:

AN:

1414306

Hom.:

Cov.:

AF XY:

0.0000257

AC XY:

AN XY:

700648

show subpopulations

Gnomad4 AFR exome

AF:

0.000303

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000512

Gnomad4 SAS exome

AF:

0.0000254

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000204

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000228

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.410C>T (p.S137L) alteration is located in exon 4 (coding exon 3) of the CCDC7 gene. This alteration results from a C to T substitution at nucleotide position 410, causing the serine (S) at amino acid position 137 to be replaced by a leucine (L). 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

0.23

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;.;T;T;T;.

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.94

.;D;D;D;D;D

M_CAP

Benign

0.0079

MetaRNN

Benign

0.32

T;T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.3

M;M;.;.;.;M

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.3

D;D;D;D;D;.

REVEL

Benign

0.25

Sift

Uncertain

0.0020

D;D;D;D;D;.

Sift4G

Uncertain

0.0070

D;D;D;D;D;.

Polyphen

1.0

.;.;D;.;.;D

Vest4

0.81

MVP

0.81

MPC

0.32

ClinPred

0.63

GERP RS

4.9

Varity_R

0.24

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: 12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over