Variant chr4-24808490-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395273.1(CCDC149):c.1507G>T(p.Asp503Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,502,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

CCDC149
NM_001395273.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0580

Variant links:

Genes affected

CCDC149 (HGNC:25405): (coiled-coil domain containing 149)

CCDC149 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18504244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC149	NM_001395273.1 linkuse as main transcript	c.1507G>T	p.Asp503Tyr	missense_variant	13/13	ENST00000635206.3	NP_001382202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC149	ENST00000635206.3 linkuse as main transcript	c.1507G>T	p.Asp503Tyr	missense_variant	13/13	5	NM_001395273.1	ENSP00000488929.2	A0A0U1RQD2
CCDC149	ENST00000502801.1 linkuse as main transcript	c.*276G>T		3_prime_UTR_variant	5/5	1		ENSP00000427529.2	A0A8V8PVV8
CCDC149	ENST00000389609.8 linkuse as main transcript	c.1489G>T	p.Asp497Tyr	missense_variant	13/13	2		ENSP00000374260.4	Q6ZUS6-5
CCDC149	ENST00000504487.5 linkuse as main transcript	c.1474G>T	p.Asp492Tyr	missense_variant	12/12	2		ENSP00000425715.2	A0A8V8PSJ6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152160

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000862

AC:

AN:

116056

Hom.:

AF XY:

0.00

AC XY:

AN XY:

59504

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:

0.0000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000481

AC:

AN:

1350558

Hom.:

Cov.:

AF XY:

0.0000514

AC XY:

AN XY:

661340

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:

0.0000586

Gnomad4 OTH exome

AF:

0.0000537

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

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

Dec 10, 2024

The c.1489G>T (p.D497Y) alteration is located in exon 13 (coding exon 12) of the CCDC149 gene. This alteration results from a G to T substitution at nucleotide position 1489, causing the aspartic acid (D) at amino acid position 497 to be replaced by a tyrosine (Y). 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

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.7

D;.;D

REVEL

Benign

0.11

Sift

Uncertain

0.010

D;.;D

Sift4G

Benign

0.079

T;D;D

Vest4

0.28

MVP

0.28

MPC

1.3

ClinPred

0.85

GERP RS

3.6

gMVP

0.22

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