Genetic Variant CCDC137:p.Ser225Ala (chr17-81672507-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_199287.3(CCDC137):c.673T>G(p.Ser225Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000449 in 1,558,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S225P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCDC137
NM_199287.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.139

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06023678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC137	NM_199287.3 link	c.673T>G	p.Ser225Ala	missense_variant	Exon 6 of 6	ENST00000329214.13	NP_954981.1	Q6PK04
CCDC137	XM_047435910.1 link	c.463T>G	p.Ser155Ala	missense_variant	Exon 6 of 6		XP_047291866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13 link	c.673T>G	p.Ser225Ala	missense_variant	Exon 6 of 6	1	NM_199287.3	ENSP00000329360.8		Q6PK04

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000606

AC:

AN:

164890

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000151

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1406742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694914

show subpopulations

African (AFR)

AF:

0.0000935

AC:

AN:

32078

American (AMR)

AF:

0.00

AC:

AN:

36684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25258

East Asian (EAS)

AF:

0.00

AC:

AN:

36498

South Asian (SAS)

AF:

0.00

AC:

AN:

79948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48808

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083448

Other (OTH)

AF:

0.00

AC:

AN:

58312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000240

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.38

CADD

Benign

8.0

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0020

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.30

.;T

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.6

M;.

PhyloP100

0.14

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.6

N;.

REVEL

Benign

0.14

Sift

Benign

0.44

T;.

Sift4G

Benign

0.74

T;T

Polyphen

0.0040

B;.

Vest4

0.041

MVP

0.58

MPC

0.057

ClinPred

0.038

GERP RS

1.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.8

Varity_R

0.043

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-81672507-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over