Variant 10-32491958-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001395015.1(CCDC7):c.833T>C(p.Met278Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,580,082 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 2 hom. )

Consequence

CCDC7
NM_001395015.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC7	NM_001395015.1 linkuse as main transcript	c.833T>C	p.Met278Thr	missense_variant	10/44	ENST00000639629.2	NP_001381944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC7	ENST00000639629.2 linkuse as main transcript	c.833T>C	p.Met278Thr	missense_variant	10/44	5	NM_001395015.1	ENSP00000491655	A2	Q96M83-1

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000390

AC:

AN:

228396

Hom.:

AF XY:

0.000411

AC XY:

AN XY:

124002

show subpopulations

Gnomad AFR exome

AF:

0.0000684

Gnomad AMR exome

AF:

0.0000694

Gnomad ASJ exome

AF:

0.00128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000516

Gnomad NFE exome

AF:

0.000581

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.000319

AC:

456

AN:

1427902

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

235

AN XY:

709416

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000102

Gnomad4 ASJ exome

AF:

0.00127

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.000628

Gnomad4 NFE exome

AF:

0.000336

Gnomad4 OTH exome

AF:

0.000255

GnomAD4 genome

AF:

0.000342

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000614

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2021

The c.833T>C (p.M278T) alteration is located in exon 10 (coding exon 9) of the CCDC7 gene. This alteration results from a T to C substitution at nucleotide position 833, causing the methionine (M) at amino acid position 278 to be replaced by a threonine (T). 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

Pathogenic

0.79

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.61

.;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

D;D;D;D;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.5

D;D;.

REVEL

Benign

0.26

Sift

Uncertain

0.0040

D;D;.

Sift4G

Benign

0.096

T;T;.

Polyphen

0.97

.;.;D

Vest4

0.78

MVP

0.50

MPC

0.38

ClinPred

0.13

GERP RS

4.1

Varity_R

0.17

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.32

Position offset: 39

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