Variant chr7-128801359-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022742.5(CCDC136):c.520G>T(p.Asp174Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000818 in 1,613,402 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 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

CCDC136
NM_022742.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3737884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC136	NM_022742.5 linkuse as main transcript	c.520G>T	p.Asp174Tyr	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.520G>T	p.Asp174Tyr	missense_variant	4/18	1	NM_022742.5	ENSP00000297788	A2	Q96JN2-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000604

AC:

AN:

248212

Hom.:

AF XY:

0.0000594

AC XY:

AN XY:

134684

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000849

AC:

124

AN:

1461230

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000248

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.0000744

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

Sep 27, 2021

The c.520G>T (p.D174Y) alteration is located in exon 4 (coding exon 4) of the CCDC136 gene. This alteration results from a G to T substitution at nucleotide position 520, causing the aspartic acid (D) at amino acid position 174 to be replaced by a tyrosine (Y). 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

0.64

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;.;.;T

Eigen

Benign

0.074

Eigen_PC

Benign

0.096

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.059

MetaRNN

Benign

0.37

T;T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.2

.;.;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.6

D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

0.96

D;.;D;D

Vest4

0.65

MVP

0.58

MPC

0.52

ClinPred

0.53

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.86

gMVP

0.30

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

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