rs547473863

Positions:

• chr7-16278181-T-A
• chr7-16278181-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001101426.4(CRPPA):​c.881A>T​(p.Asp294Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.837

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.881A>T	p.Asp294Val	missense_variant	6/10	ENST00000407010.7	NP_001094896.1
CRPPA	NM_001368197.1	c.776A>T	p.Asp259Val	missense_variant	5/9		NP_001355126.1
CRPPA	NM_001101417.4	c.731A>T	p.Asp244Val	missense_variant	5/9		NP_001094887.1
CRPPA	NR_160656.1	n.946A>T		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRPPA	ENST00000407010.7	c.881A>T	p.Asp294Val	missense_variant	6/10	5	NM_001101426.4	ENSP00000385478	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000431 AC: 1 AN: 232016 Hom.: 0 AF XY: 0.00000794 AC XY: 1 AN XY: 125876

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000176

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431396 Hom.: 0 Cov.: 25 AF XY: 0.00000140 AC XY: 1 AN XY: 712452

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: 0.0000169

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.93	P;.
Vest4		0.49
MutPred		0.59		Loss of disorder (P = 0.0347);.;
MVP		0.78
MPC		0.12
ClinPred		0.25	T
GERP RS		2.5
Varity_R		0.39
gMVP		0.57

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: rs547473863; hg19: chr7-16317806;