Variant 4-24836508-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001395273.1(CCDC149):c.648G>T(p.Arg216Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,600,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CCDC149
NM_001395273.1 missense, splice_region

Scores

Splicing: ADA: 0.2327

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

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

CCDC149 links:

CCDC149 (HGNC:):

CCDC149 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC149	NM_001395273.1 linkuse as main transcript	c.648G>T	p.Arg216Ser	missense_variant, splice_region_variant	7/13	ENST00000635206.3	NP_001382202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC149	ENST00000635206.3 linkuse as main transcript	c.648G>T	p.Arg216Ser	missense_variant, splice_region_variant	7/13	5	NM_001395273.1	ENSP00000488929.2		A0A0U1RQD2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151962

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:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1448222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721152

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:

9.08e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151962

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74198

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:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Oct 29, 2024

The c.663G>T (p.R221S) alteration is located in exon 8 (coding exon 7) of the CCDC149 gene. This alteration results from a G to T substitution at nucleotide position 663, causing the arginine (R) at amino acid position 221 to be replaced by a serine (S). 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

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Benign

0.40

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.92

D;D;D

MetaSVM

Benign

-0.52

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.5

D;.;D

REVEL

Pathogenic

0.77

Sift

Uncertain

0.0020

D;.;D

Sift4G

Uncertain

0.0090

D;D;D

Vest4

0.92

MVP

0.37

MPC

1.6

ClinPred

0.99

GERP RS

1.2

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.23

dbscSNV1_RF

Benign

0.44

SpliceAI score (max)

0.14

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