rs886042489

Variant names:

• chr7-16421130-G-A
• rs886042489
• NM_001101426.4:c.193C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-16421130-G-A
• chr7-16421130-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001101426.4(CRPPA):​c.193C>T​(p.Pro65Ser) 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.65

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]

LOC105375168 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.902

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.193C>T	p.Pro65Ser	missense_variant	Exon 1 of 10	ENST00000407010.7	NP_001094896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.193C>T	p.Pro65Ser	missense_variant	Exon 1 of 10	5	NM_001101426.4	ENSP00000385478.2
CRPPA	ENST00000399310.3	c.193C>T	p.Pro65Ser	missense_variant	Exon 1 of 9	1		ENSP00000382249.3
CRPPA	ENST00000675257.1	c.-46-14793C>T		intron_variant	Intron 2 of 9			ENSP00000501664.1
CRPPA	ENST00000674759.1	c.-46-14793C>T		intron_variant	Intron 2 of 9			ENSP00000502749.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1175846 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 566854

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 17, 2015

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.72	D;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Pathogenic	0.84	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.5	D;D
REVEL	Pathogenic	0.83
Sift	Benign	0.041	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	D;.
Vest4		0.64
MutPred		0.79		Loss of phosphorylation at T64 (P = 0.0997);Loss of phosphorylation at T64 (P = 0.0997);
MVP		0.67
MPC		0.35
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.77
gMVP		0.77

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: rs886042489; hg19: chr7-16460755;