Variant 7-128801491-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022742.5(CCDC136):c.652G>C(p.Asp218His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,603,782 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0073 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 142 hom. )

Consequence

CCDC136
NM_022742.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.47

Variant links:

Genes affected

CCDC136 (HGNC:22225): (coiled-coil domain containing 136) Predicted to be involved in acrosome assembly and single fertilization. Predicted to be integral component of membrane. Predicted to be active in acrosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC136 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025648475).

BP6

Variant 7-128801491-G-C is Benign according to our data. Variant chr7-128801491-G-C is described in ClinVar as [Benign]. Clinvar id is 719137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00726 (1105/152254) while in subpopulation SAS AF= 0.0307 (148/4814). AF 95% confidence interval is 0.0267. There are 9 homozygotes in gnomad4. There are 561 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC136	NM_022742.5 linkuse as main transcript	c.652G>C	p.Asp218His	missense_variant	4/18	ENST00000297788.9	NP_073579.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC136	ENST00000297788.9 linkuse as main transcript	c.652G>C	p.Asp218His	missense_variant	4/18	1	NM_022742.5	ENSP00000297788	A2	Q96JN2-1

Frequencies

GnomAD3 genomes

AF:

0.00724

AC:

1102

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0255

Gnomad SAS

AF:

0.0307

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00682

AC:

1655

AN:

242530

Hom.:

AF XY:

0.00755

AC XY:

996

AN XY:

131882

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.000910

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0149

Gnomad SAS exome

AF:

0.0331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000744

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00422

AC:

6132

AN:

1451528

Hom.:

142

Cov.:

AF XY:

0.00492

AC XY:

3542

AN XY:

719830

show subpopulations

Gnomad4 AFR exome

AF:

0.0184

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0450

Gnomad4 SAS exome

AF:

0.0316

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000565

Gnomad4 OTH exome

AF:

0.00575

GnomAD4 genome

AF:

0.00726

AC:

1105

AN:

152254

Hom.:

Cov.:

AF XY:

0.00754

AC XY:

561

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0176

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0256

Gnomad4 SAS

AF:

0.0307

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00223

Hom.:

Bravo

AF:

0.00716

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.000485

AC:

ExAC

AF:

0.00733

AC:

885

Asia WGS

AF:

0.0350

AC:

120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;.;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;D;D

MetaRNN

Benign

0.0026

T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.3

.;.;M

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.31

MVP

0.70

MPC

0.50

ClinPred

0.034

GERP RS

5.2

Varity_R

0.23

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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