Variant 17-81672507-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_199287.3(CCDC137):c.673T>C(p.Ser225Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,406,740 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: 0.0000021 ( 0 hom. )

Consequence

CCDC137
NM_199287.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.139

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061421454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC137	NM_199287.3 linkuse as main transcript	c.673T>C	p.Ser225Pro	missense_variant	6/6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1 linkuse as main transcript	c.463T>C	p.Ser155Pro	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.673T>C	p.Ser225Pro	missense_variant	6/6	1	NM_199287.3	ENSP00000329360	P1
CCDC137	ENST00000574107.1 linkuse as main transcript	c.700T>C	p.Ser234Pro	missense_variant	7/7	3		ENSP00000458350
CCDC137	ENST00000575223.5 linkuse as main transcript	c.673T>C	p.Ser225Pro	missense_variant, NMD_transcript_variant	6/7	5		ENSP00000458884
CCDC137	ENST00000571916.1 linkuse as main transcript	c.*308T>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	3		ENSP00000460261

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

164890

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

88146

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000302

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1406740

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

694912

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000277

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 08, 2024

The c.673T>C (p.S225P) alteration is located in exon 6 (coding exon 6) of the CCDC137 gene. This alteration results from a T to C substitution at nucleotide position 673, causing the serine (S) at amino acid position 225 to be replaced by a proline (P). 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

0.088

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0022

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.44

.;T

M_CAP

Benign

0.082

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.15

Sift

Benign

0.26

T;.

Sift4G

Benign

0.30

T;T

Polyphen

0.017

B;.

Vest4

0.056

MutPred

0.20

Loss of phosphorylation at S225 (P = 0.01);.;

MVP

0.67

MPC

0.077

ClinPred

0.018

GERP RS

1.4

Varity_R

0.19

gMVP

0.18

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