Variant 17-81672649-T-C 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.815T>C(p.Leu272Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,601,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

CCDC137
NM_199287.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.158

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=0.042563707).

BS2

High AC in GnomAdExome4 at 79 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC137	NM_199287.3 linkuse as main transcript	c.815T>C	p.Leu272Pro	missense_variant	6/6	ENST00000329214.13	NP_954981.1
CCDC137	XM_047435910.1 linkuse as main transcript	c.605T>C	p.Leu202Pro	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.815T>C	p.Leu272Pro	missense_variant	6/6	1	NM_199287.3	ENSP00000329360	P1
CCDC137	ENST00000574107.1 linkuse as main transcript	c.842T>C	p.Leu281Pro	missense_variant	7/7	3		ENSP00000458350
CCDC137	ENST00000575223.5 linkuse as main transcript	c.815T>C	p.Leu272Pro	missense_variant, NMD_transcript_variant	6/7	5		ENSP00000458884
CCDC137	ENST00000571916.1 linkuse as main transcript	c.*450T>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	3		ENSP00000460261

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000224

AC:

AN:

223142

Hom.:

AF XY:

0.0000247

AC XY:

AN XY:

121698

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:

0.0000539

Gnomad NFE exome

AF:

0.0000300

Gnomad OTH exome

AF:

0.000184

GnomAD4 exome

AF:

0.0000545

AC:

AN:

1449008

Hom.:

Cov.:

AF XY:

0.0000597

AC XY:

AN XY:

719758

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

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:

0.0000390

Gnomad4 NFE exome

AF:

0.0000659

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000333

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

Jan 09, 2024

The c.815T>C (p.L272P) 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 815, causing the leucine (L) at amino acid position 272 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

0.059

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.27

CADD

Benign

0.17

DANN

Benign

0.64

DEOGEN2

Benign

0.0039

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.37

.;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.49

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.88

N;.

REVEL

Uncertain

0.40

Sift

Benign

0.22

T;.

Sift4G

Benign

0.24

T;T

Polyphen

0.0

B;.

Vest4

0.056

MutPred

0.20

Gain of loop (P = 0.0045);.;

MVP

0.15

MPC

0.094

ClinPred

0.029

GERP RS

-6.3

Varity_R

0.15

gMVP

0.18

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