7-16308536-G-C

Variant names:

• chr7-16308536-G-C
• rs369193825
• NM_001101426.4:c.776C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001101426.4(CRPPA):​c.776C>G​(p.Pro259Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.10

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.776C>G	p.Pro259Arg	missense_variant	Exon 4 of 10	ENST00000407010.7	NP_001094896.1
CRPPA	NM_001101417.4	c.626C>G	p.Pro209Arg	missense_variant	Exon 3 of 9		NP_001094887.1
CRPPA	NM_001368197.1	c.685-7070C>G		intron_variant	Intron 3 of 8		NP_001355126.1
CRPPA	NR_160656.1	n.901-30310C>G		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.776C>G	p.Pro259Arg	missense_variant	Exon 4 of 10	5	NM_001101426.4	ENSP00000385478.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.62
Sift	Benign	0.20	T;D
Sift4G	Benign	0.11	T;D
Polyphen		0.72	P;.
Vest4		0.60
MutPred		0.57		Gain of MoRF binding (P = 0.0037);.;
MVP		0.72
MPC		0.18
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.70
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs369193825; hg19: chr7-16348161;