NM_001101426.4:c.1017T>C

Variant names:

• chr7-16258929-A-G
• rs773884120
• NM_001101426.4:c.1017T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001101426.4(CRPPA):​c.1017T>C​(p.Val339Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. V339V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CRPPA NM_001101426.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 7-16258929-A-G is Benign according to our data. Variant chr7-16258929-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 473154.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.4 with no splicing effect.

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.1017T>C	p.Val339Val	synonymous	Exon 7 of 10	NP_001094896.1
	CRPPA	NM_001368197.1		c.912T>C	p.Val304Val	synonymous	Exon 6 of 9	NP_001355126.1
	CRPPA	NM_001101417.4		c.867T>C	p.Val289Val	synonymous	Exon 6 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.1017T>C	p.Val339Val	synonymous	Exon 7 of 10	ENSP00000385478.2
	CRPPA	ENST00000399310.3	TSL:1	c.867T>C	p.Val289Val	synonymous	Exon 6 of 9	ENSP00000382249.3
	CRPPA-AS1	ENST00000438573.5	TSL:1	n.222-2970A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 244494 AF XY: 0.00000754

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455796 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724086

African (AFR) AF: 0.00 AC: 0 AN: 33268

American (AMR) AF: 0.00 AC: 0 AN: 44024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 85354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1108642

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000434 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.6
DANN	Benign	0.88
PhyloP100		2.4

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

Other links and lift over

dbSNP: rs773884120; hg19: chr7-16298554;