chr15-22786671-T-TGCGGCA

Position:

• chr15-22786671-T-TGCGGCA

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_144599.5(NIPA1):​c.21_26dup​(p.Ala15_Ala16dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000045 in 1,065,912 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: NIPA1 NM_144599.5 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_144599.5
• BP6: Variant 15-22786671-T-TGCGGCA is Benign according to our data. Variant chr15-22786671-T-TGCGGCA is described in ClinVar as [Benign]. Clinvar id is 1474382.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA1	NM_144599.5	c.21_26dup	p.Ala15_Ala16dup	inframe_insertion	1/5	ENST00000337435.9
NIPA1	NM_001142275.1	c.-48+429_-48+434dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA1	ENST00000337435.9	c.21_26dup	p.Ala15_Ala16dup	inframe_insertion	1/5	1	NM_144599.5	P1
NIPA1	ENST00000437912.6	c.-48+12364_-48+12369dup		intron_variant		1
NIPA1	ENST00000561183.5	c.-48+429_-48+434dup		intron_variant		1
NIPA1	ENST00000560069.5	n.31+429_31+434dup		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0000360 AC: 5 AN: 138958 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000732

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000222

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000467

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000464 AC: 43 AN: 926954 Hom.: 0 Cov.: 21 AF XY: 0.0000496 AC XY: 22 AN XY: 443682

Gnomad4 AFR exome AF: 0.0000569

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000427

Gnomad4 OTH exome AF: 0.000122

GnomAD4 genome AF: 0.0000360 AC: 5 AN: 138958 Hom.: 0 Cov.: 30 AF XY: 0.0000148 AC XY: 1 AN XY: 67372

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000732

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000222

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000467

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 6 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 09, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555371600; hg19: chr15-23086397;