dbSNP rs776384867: CCDC137:p.Ala2Glu (chr17-81666771-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_199287.3(CCDC137):c.5C>A(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,314,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A2S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CCDC137
NM_199287.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65

Publications

1 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:

OXLD1 (HGNC:27901): (oxidoreductase like domain containing 1)

OXLD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17406553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC137	NM_199287.3 link	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 6	ENST00000329214.13	NP_954981.1	Q6PK04
OXLD1	NM_001039842.3 link	c.-194G>T		upstream_gene_variant		ENST00000374741.4	NP_001034931.1	Q5BKU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC137	ENST00000329214.13 link	c.5C>A	p.Ala2Glu	missense_variant	Exon 1 of 6	1	NM_199287.3	ENSP00000329360.8		Q6PK04
OXLD1	ENST00000374741.4 link	c.-194G>T		upstream_gene_variant		1	NM_001039842.3	ENSP00000363873.3		Q5BKU9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000778

AC:

AN:

128522

AF XY:

0.0000138

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:

0.0000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000152

AC:

AN:

1314450

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

647672

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26404

American (AMR)

AF:

0.00

AC:

AN:

23994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19626

East Asian (EAS)

AF:

0.00

AC:

AN:

31620

South Asian (SAS)

AF:

0.00

AC:

AN:

67232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4920

European-Non Finnish (NFE)

AF:

9.56e-7

AC:

AN:

1045734

Other (OTH)

AF:

0.0000186

AC:

AN:

53632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000834

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Benign

6.4

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0016

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.30

.;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

PhyloP100

-1.7

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.2

N;.

REVEL

Benign

0.071

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.095

B;.

Vest4

0.24

MutPred

0.29

Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);

MVP

0.17

MPC

0.068

ClinPred

0.54

GERP RS

0.87

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.53

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over