7-16376129-G-T

Variant names:

• chr7-16376129-G-T
• rs387907160
• NM_001101426.4:c.647C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001101426.4(CRPPA):​c.647C>A​(p.Ala216Asp) 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: 32)
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.28

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95
• PP5: Variant 7-16376129-G-T is Pathogenic according to our data. Variant chr7-16376129-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 31565.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-16376129-G-T is described in Lovd as [Pathogenic]. Variant chr7-16376129-G-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.647C>A	p.Ala216Asp	missense_variant	Exon 3 of 10	ENST00000407010.7	NP_001094896.1
CRPPA	NM_001368197.1	c.647C>A	p.Ala216Asp	missense_variant	Exon 3 of 9		NP_001355126.1
CRPPA	NM_001101417.4	c.534+29932C>A		intron_variant	Intron 2 of 8		NP_001094887.1
CRPPA	NR_160656.1	n.863C>A		non_coding_transcript_exon_variant	Exon 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.647C>A	p.Ala216Asp	missense_variant	Exon 3 of 10	5	NM_001101426.4	ENSP00000385478.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

May 01, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Pathogenic	3.5	M
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.73		Loss of catalytic residue at A216 (P = 0.069);
MVP		0.76
MPC		0.42
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.99
gMVP		0.90

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: rs387907160; hg19: chr7-16415754;