GeneBe

rs759189333

Variant names:

Variant summary

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

The NM_001258306.3(CCDC74A):​c.34C>G​(p.Pro12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. P12S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CCDC74A
NM_001258306.3 missense

Scores

1
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.122

Publications

0 publications found
Variant links:
Genes affected
CCDC74A (HGNC:25197): (coiled-coil domain containing 74A)

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=0.19886899).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258306.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CCDC74A
NM_001258306.3
MANE Select
c.34C>Gp.Pro12Ala
missense
Exon 1 of 8NP_001245235.1Q96AQ1-2
CCDC74A
NM_001349042.2
c.34C>Gp.Pro12Ala
missense
Exon 1 of 8NP_001335971.1
CCDC74A
NM_138770.4
c.34C>Gp.Pro12Ala
missense
Exon 1 of 8NP_620125.1Q96AQ1-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
CCDC74A
ENST00000409856.8
TSL:1 MANE Select
c.34C>Gp.Pro12Ala
missense
Exon 1 of 8ENSP00000387009.3Q96AQ1-2
CCDC74A
ENST00000295171.10
TSL:1
c.34C>Gp.Pro12Ala
missense
Exon 1 of 8ENSP00000295171.6Q96AQ1-1
CCDC74A
ENST00000467992.6
TSL:1
c.34C>Gp.Pro12Ala
missense
Exon 1 of 7ENSP00000444610.2F5GZA4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1310084
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
638408
African (AFR)
AF:
0.00
AC:
0
AN:
28700
American (AMR)
AF:
0.00
AC:
0
AN:
20662
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19196
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35366
South Asian (SAS)
AF:
0.00
AC:
0
AN:
64752
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
44600
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3640
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1039160
Other (OTH)
AF:
0.00
AC:
0
AN:
54008
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.050
T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.073
N
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L
PhyloP100
-0.12
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.052
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.069
T
Polyphen
1.0
D
Vest4
0.17
MutPred
0.18
Loss of glycosylation at P12 (P = 0.0091)
MVP
0.24
MPC
1.3
ClinPred
0.74
D
GERP RS
2.0
PromoterAI
-0.0070
Neutral
Varity_R
0.093
gMVP
0.15
Mutation Taster
=92/8
polymorphism

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

Other links and lift over

dbSNP: rs759189333; hg19: chr2-132285577; API