Genetic Variant CCDC148:p.Ala448Thr (chr2-158220623-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_138803.4(CCDC148):c.1342G>A(p.Ala448Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,603,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

CCDC148
NM_138803.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

CCDC148 (HGNC:25191): (coiled-coil domain containing 148)

CCDC148 links:

CCDC148-AS1 (HGNC:44134): (CCDC148 antisense RNA 1)

CCDC148-AS1 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=0.096453756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC148	NM_138803.4 link	c.1342G>A	p.Ala448Thr	missense_variant	Exon 11 of 14	ENST00000283233.10	NP_620158.3	Q8NFR7-1
CCDC148	NM_001301684.2 link	c.904G>A	p.Ala302Thr	missense_variant	Exon 9 of 12		NP_001288613.1	Q8NFR7
CCDC148-AS1	NR_038850.1 link	n.355+13006C>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC148	ENST00000283233.10 link	c.1342G>A	p.Ala448Thr	missense_variant	Exon 11 of 14	1	NM_138803.4	ENSP00000283233.5		Q8NFR7-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

240938

Hom.:

AF XY:

0.000146

AC XY:

AN XY:

130164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000187

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000228

Gnomad SAS exome

AF:

0.000434

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000451

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000909

AC:

132

AN:

1451730

Hom.:

Cov.:

AF XY:

0.0000984

AC XY:

AN XY:

721840

show subpopulations

Gnomad4 AFR exome

AF:

0.0000610

Gnomad4 AMR exome

AF:

0.000118

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000204

Gnomad4 SAS exome

AF:

0.000323

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000748

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000105

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000590

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000774

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000988

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.026

T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.055

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.12

T;T

Polyphen

0.87

P;P

Vest4

0.31

MVP

0.48

MPC

0.072

ClinPred

0.068

GERP RS

4.6

Varity_R

0.074

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over