Genetic Variant CCDC74A:p.Pro12Ala (chr2-131528004-C-G) – 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_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

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)

CCDC74A 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=0.19886899).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC74A	NM_001258306.3	MANE Select	c.34C>G	p.Pro12Ala	missense	Exon 1 of 8	NP_001245235.1	Q96AQ1-2
CCDC74A	NM_001349042.2		c.34C>G	p.Pro12Ala	missense	Exon 1 of 8	NP_001335971.1
CCDC74A	NM_138770.4		c.34C>G	p.Pro12Ala	missense	Exon 1 of 8	NP_620125.1	Q96AQ1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC74A	ENST00000409856.8	TSL:1 MANE Select	c.34C>G	p.Pro12Ala	missense	Exon 1 of 8	ENSP00000387009.3	Q96AQ1-2
CCDC74A	ENST00000295171.10	TSL:1	c.34C>G	p.Pro12Ala	missense	Exon 1 of 8	ENSP00000295171.6	Q96AQ1-1
CCDC74A	ENST00000467992.6	TSL:1	c.34C>G	p.Pro12Ala	missense	Exon 1 of 7	ENSP00000444610.2	F5GZA4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1310084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

638408

African (AFR)

AF:

0.00

AC:

AN:

28700

American (AMR)

AF:

0.00

AC:

AN:

20662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19196

East Asian (EAS)

AF:

0.00

AC:

AN:

35366

South Asian (SAS)

AF:

0.00

AC:

AN:

64752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3640

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1039160

Other (OTH)

AF:

0.00

AC:

AN:

54008

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.80

M_CAP

Benign

0.039

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-0.12

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.052

Sift

Pathogenic

0.0

Sift4G

Benign

0.069

Polyphen

1.0

Vest4

0.17

MutPred

0.18

Loss of glycosylation at P12 (P = 0.0091)

MVP

0.24

MPC

1.3

ClinPred

0.74

GERP RS

2.0

PromoterAI

-0.0070

Neutral

(source)

Varity_R

0.093

gMVP

0.15

Mutation Taster

=92/8

polymorphism

(source)

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

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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