rs958075

Positions:

• chr20-25614487-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000304788.4(NANP):​c.*1438C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,756 control chromosomes in the GnomAD database, including 10,888 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10888 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: NANP ENST00000304788.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

Genes affected

NANP (HGNC:16140): (N-acetylneuraminic acid phosphatase) Enables N-acylneuraminate-9-phosphatase activity. Involved in N-acetylneuraminate biosynthetic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NANP	NM_152667.3	c.*1438C>T		3_prime_UTR_variant	2/2	ENST00000304788.4	NP_689880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NANP	ENST00000304788.4	c.*1438C>T		3_prime_UTR_variant	2/2	1	NM_152667.3	ENSP00000302441	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54948 AN: 151640 Hom.: 10882 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.400

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.362 AC: 54967 AN: 151756 Hom.: 10888 Cov.: 32 AF XY: 0.362 AC XY: 26803 AN XY: 74142

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.0157

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.399

Alfa AF: 0.398 Hom.: 3722

Bravo AF: 0.361

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.68

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: rs958075; hg19: chr20-25595123;