15-22777657-T-C

Position:

• chr15-22777657-T-C

Variant summary

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

The ENST00000437912.6(NIPA1):​c.-48+3344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,902 control chromosomes in the GnomAD database, including 5,627 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 0.26 (5627 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: NIPA1 ENST00000437912.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

Genes affected

NIPA1 (HGNC:17043): (NIPA magnesium transporter 1) This gene encodes a magnesium transporter that associates with early endosomes and the cell surface in a variety of neuronal and epithelial cells. This protein may play a role in nervous system development and maintenance. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with autosomal dominant spastic paraplegia 6. [provided by RefSeq, Nov 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC283683	NR_040057.1	n.475-110T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA1	ENST00000437912.6	c.-48+3344T>C		intron_variant		1
	ENST00000619611.4	n.475-110T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39057 AN: 151774 Hom.: 5616 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.257 AC: 39108 AN: 151892 Hom.: 5627 Cov.: 32 AF XY: 0.262 AC XY: 19445 AN XY: 74226

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.225

Alfa AF: 0.135 Hom.: 325

Bravo AF: 0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8040695; hg19: chr15-23095411;