Genetic Variant NM_001101426.4:c.13C>A (chr7-16421310-G-T) – 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_001101426.4(CRPPA):c.13C>A(p.Pro5Thr) 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. 14/21 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. P5S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CRPPA
NM_001101426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

0 publications found

Variant links:

Genes affected

CRPPA (HGNC:37276): (CDP-L-ribitol pyrophosphorylase A) This gene encodes a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein. Mutations in this gene are the cause of Walker-Warburg syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

CRPPA Gene-Disease associations (from GenCC):

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
myopathy caused by variation in CRPPA
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2U
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy without intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CRPPA links:

ENSG00000272537 (HGNC:):

ENSG00000272537 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=0.09449318).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CRPPA	NM_001101426.4	MANE Select	c.13C>A	p.Pro5Thr	missense	Exon 1 of 10	NP_001094896.1
CRPPA	NM_001368197.1		c.13C>A	p.Pro5Thr	missense	Exon 1 of 9	NP_001355126.1
CRPPA	NM_001101417.4		c.13C>A	p.Pro5Thr	missense	Exon 1 of 9	NP_001094887.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CRPPA	ENST00000407010.7	TSL:5 MANE Select	c.13C>A	p.Pro5Thr	missense	Exon 1 of 10	ENSP00000385478.2
CRPPA	ENST00000399310.3	TSL:1	c.13C>A	p.Pro5Thr	missense	Exon 1 of 9	ENSP00000382249.3
CRPPA	ENST00000675257.1		c.-46-14973C>A		intron	N/A	ENSP00000501664.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1108240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

526700

African (AFR)

AF:

0.00

AC:

AN:

22792

American (AMR)

AF:

0.00

AC:

AN:

8294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14584

East Asian (EAS)

AF:

0.00

AC:

AN:

26312

South Asian (SAS)

AF:

0.00

AC:

AN:

26376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2956

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

930626

Other (OTH)

AF:

0.00

AC:

AN:

44286

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.51

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.0

PhyloP100

1.5

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.2

REVEL

Benign

0.17

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.036

Polyphen

0.0010

Vest4

0.16

MutPred

0.26

Gain of phosphorylation at P5 (P = 0.0031)

MVP

0.21

MPC

0.073

ClinPred

0.12

GERP RS

-0.18

PromoterAI

-0.23

Neutral

(source)

Varity_R

0.081

gMVP

0.27

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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