Variant 17-81672552-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_199287.3(CCDC137):c.718C>T(p.Pro240Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,418,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CCDC137
NM_199287.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.732

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022771388).

BS2

High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC137	NM_199287.3 linkuse as main transcript	c.718C>T	p.Pro240Ser	missense_variant	6/6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1 linkuse as main transcript	c.508C>T	p.Pro170Ser	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.718C>T	p.Pro240Ser	missense_variant	6/6	1	NM_199287.3	ENSP00000329360	P1
CCDC137	ENST00000574107.1 linkuse as main transcript	c.745C>T	p.Pro249Ser	missense_variant	7/7	3		ENSP00000458350
CCDC137	ENST00000575223.5 linkuse as main transcript	c.718C>T	p.Pro240Ser	missense_variant, NMD_transcript_variant	6/7	5		ENSP00000458884
CCDC137	ENST00000571916.1 linkuse as main transcript	c.*353C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	3		ENSP00000460261

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000613

AC:

AN:

179314

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

96480

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000451

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000162

AC:

AN:

1418796

Hom.:

Cov.:

AF XY:

0.0000199

AC XY:

AN XY:

701920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000284

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.0000421

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

Jun 16, 2024

The c.718C>T (p.P240S) alteration is located in exon 6 (coding exon 6) of the CCDC137 gene. This alteration results from a C to T substitution at nucleotide position 718, causing the proline (P) at amino acid position 240 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.5

DANN

Benign

0.64

DEOGEN2

Benign

0.0024

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.66

.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.12

Sift

Benign

0.36

T;.

Sift4G

Benign

0.37

T;T

Polyphen

0.035

B;.

Vest4

0.046

MutPred

0.14

Gain of MoRF binding (P = 0.0364);.;

MVP

0.67

MPC

0.076

ClinPred

0.036

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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