dbSNP rs191079849: CCDC149:p.Asp392Val (chr4-24819861-T-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_001395273.1(CCDC149):c.1175A>T(p.Asp392Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D392G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CCDC149
NM_001395273.1 missense, splice_region

Scores

Splicing: ADA: 0.0005663

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.363

Publications

0 publications found

Variant links:

Genes affected

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

CCDC149 links:

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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=0.07341963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395273.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC149	NM_001395273.1	MANE Select	c.1175A>T	p.Asp392Val	missense splice_region	Exon 12 of 13	NP_001382202.1	A0A0U1RQD2
CCDC149	NM_173463.6		c.1157A>T	p.Asp386Val	missense splice_region	Exon 12 of 13	NP_775734.2	Q6ZUS6-5
CCDC149	NM_001130726.5		c.1142A>T	p.Asp381Val	missense splice_region	Exon 11 of 12	NP_001124198.2	A0A8V8PSJ6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC149	ENST00000635206.3	TSL:5 MANE Select	c.1175A>T	p.Asp392Val	missense splice_region	Exon 12 of 13	ENSP00000488929.2	A0A0U1RQD2
CCDC149	ENST00000502801.1	TSL:1	c.358-11042A>T		intron	N/A	ENSP00000427529.2	A0A8V8PVV8
CCDC149	ENST00000904727.1		c.1166A>T	p.Asp389Val	missense splice_region	Exon 12 of 13	ENSP00000574786.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000639

AC:

AN:

156526

AF XY:

0.0000121

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:

0.0000165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398324

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689764

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31572

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077988

Other (OTH)

AF:

0.00

AC:

AN:

57964

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Benign

0.87

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.80

M_CAP

Benign

0.0066

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.1

PhyloP100

0.36

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

REVEL

Benign

0.020

Sift

Benign

0.11

Sift4G

Benign

0.28

Vest4

0.22

MVP

0.095

MPC

0.85

ClinPred

0.073

GERP RS

2.0

gMVP

0.37

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00057

dbscSNV1_RF

Benign

0.18

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.99

Position offset: 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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over