7-16258392-AAAC-AAACAAC

Variant names:

• chr7-16258392-A-AAAC
• rs587777798
• NM_001101426.4:c.1114_1116dupGTT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001101426.4(CRPPA):​c.1114_1116dupGTT​(p.Val372dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRPPA NM_001101426.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 6 publications found

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]

CRPPA-AS1 (HGNC:48962): (CRPPA antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001101426.4. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	NM_001101426.4	MANE Select	c.1114_1116dupGTT	p.Val372dup	conservative_inframe_insertion	Exon 8 of 10	NP_001094896.1
	CRPPA	NM_001368197.1		c.1009_1011dupGTT	p.Val337dup	conservative_inframe_insertion	Exon 7 of 9	NP_001355126.1
	CRPPA	NM_001101417.4		c.964_966dupGTT	p.Val322dup	conservative_inframe_insertion	Exon 7 of 9	NP_001094887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	ENST00000407010.7	TSL:5 MANE Select	c.1114_1116dupGTT	p.Val372dup	conservative_inframe_insertion	Exon 8 of 10	ENSP00000385478.2
	CRPPA	ENST00000399310.3	TSL:1	c.964_966dupGTT	p.Val322dup	conservative_inframe_insertion	Exon 7 of 9	ENSP00000382249.3
	CRPPA-AS1	ENST00000438573.5	TSL:1	n.222-3496_222-3494dupACA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587777798; hg19: chr7-16298017; COSMIC: COSV101235477;