rs387907162

chr7-16406231-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001101426.4(CRPPA):c.364G>C(p.Ala122Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864
• PP5: Variant 7-16406231-C-G is Pathogenic according to our data. Variant chr7-16406231-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 31567.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-16406231-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRPPA	NM_001101426.4	c.364G>C	p.Ala122Pro	missense_variant	2/10	ENST00000407010.7
CRPPA	NM_001368197.1	c.364G>C	p.Ala122Pro	missense_variant	2/9
CRPPA	NM_001101417.4	c.364G>C	p.Ala122Pro	missense_variant	2/9
CRPPA	NR_160656.1	n.580G>C		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRPPA	ENST00000407010.7	c.364G>C	p.Ala122Pro	missense_variant	2/10	5	NM_001101426.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	0.89	D;D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.96	D;.
Vest4		0.80
MutPred		0.86		Loss of catalytic residue at A122 (P = 0.0278);Loss of catalytic residue at A122 (P = 0.0278);
MVP		0.65
MPC		0.29
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.92
gMVP		0.84

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

LitVar

Other links and lift over

dbSNP: rs387907162; hg19: chr7-16445856;