Variant 17-81672625-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_199287.3(CCDC137):c.791C>T(p.Ala264Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,599,344 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

CCDC137
NM_199287.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.306

Variant links:

Genes affected

CCDC137 (HGNC:33451): (coiled-coil domain containing 137) Enables RNA binding activity. Located in chromosome and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

CCDC137 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035168797).

BP6

Variant 17-81672625-C-T is Benign according to our data. Variant chr17-81672625-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2592618.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC137	NM_199287.3 linkuse as main transcript	c.791C>T	p.Ala264Val	missense_variant	6/6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1 linkuse as main transcript	c.581C>T	p.Ala194Val	missense_variant	6/6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCDC137	ENST00000329214.13 linkuse as main transcript	c.791C>T	p.Ala264Val	missense_variant	6/6	1	NM_199287.3	ENSP00000329360	P1
CCDC137	ENST00000574107.1 linkuse as main transcript	c.818C>T	p.Ala273Val	missense_variant	7/7	3		ENSP00000458350
CCDC137	ENST00000575223.5 linkuse as main transcript	c.791C>T	p.Ala264Val	missense_variant, NMD_transcript_variant	6/7	5		ENSP00000458884
CCDC137	ENST00000571916.1 linkuse as main transcript	c.*426C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	3		ENSP00000460261

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000109

AC:

AN:

219904

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

119662

show subpopulations

Gnomad AFR exome

AF:

0.000235

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.000372

GnomAD4 exome

AF:

0.0000981

AC:

142

AN:

1447110

Hom.:

Cov.:

AF XY:

0.0000905

AC XY:

AN XY:

718552

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000330

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000772

Gnomad4 SAS exome

AF:

0.0000239

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000986

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000315

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.000408

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.0000332

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Benign

1.8

DANN

Benign

0.81

DEOGEN2

Benign

0.0056

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.41

.;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.73

N;.

REVEL

Benign

0.29

Sift

Benign

0.31

T;.

Sift4G

Benign

0.30

T;T

Polyphen

0.0010

B;.

Vest4

0.071

MVP

0.46

MPC

0.063

ClinPred

0.030

GERP RS

0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.089

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