NM_001101426.4:c.67G>A

Variant names:

• chr7-16421256-C-T
• NM_001101426.4:c.67G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001101426.4(CRPPA):​c.67G>A​(p.Gly23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000172 in 1,162,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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: 0.0000017 (0 hom.)
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27418733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRPPA	NM_001101426.4	c.67G>A	p.Gly23Ser	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.67G>A	p.Gly23Ser	missense_variant	Exon 1 of 10	5	NM_001101426.4	ENSP00000385478.2
CRPPA	ENST00000399310.3	c.67G>A	p.Gly23Ser	missense_variant	Exon 1 of 9	1		ENSP00000382249.3
CRPPA	ENST00000675257.1	c.-46-14919G>A		intron_variant	Intron 2 of 9			ENSP00000501664.1
CRPPA	ENST00000674759.1	c.-46-14919G>A		intron_variant	Intron 2 of 9			ENSP00000502749.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000172 AC: 2 AN: 1162552 Hom.: 0 Cov.: 31 AF XY: 0.00000179 AC XY: 1 AN XY: 558362

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: 0.00000209

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0053	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.60	T;T
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.28
Sift	Uncertain	0.014	D;D
Sift4G	Benign	0.20	T;T
Polyphen		0.98	D;.
Vest4		0.055
MutPred		0.29		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.64
MPC		0.057
ClinPred		0.31	T
GERP RS		4.0
Varity_R		0.13
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-16460881;