15-22786671-T-TGCG

Position:

• chr15-22786671-T-TGCG

Variant summary

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

The NM_144599.5(NIPA1):​c.18_20dupGGC​(p.Ala7dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000485 in 926,956 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: NIPA1 NM_144599.5 disruptive_inframe_insertion
• Clinical Significance: Likely 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-TGCG is Benign according to our data. Variant chr15-22786671-T-TGCG is described in ClinVar as [Likely_benign]. Clinvar id is 3668459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPA1	NM_144599.5	c.18_20dupGGC	p.Ala7dup	disruptive_inframe_insertion	1/5	ENST00000337435.9	NP_653200.2
NIPA1	NM_001142275.1	c.-48+426_-48+428dupGGC		intron_variant			NP_001135747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPA1	ENST00000337435.9	c.18_20dupGGC	p.Ala7dup	disruptive_inframe_insertion	1/5	1	NM_144599.5	ENSP00000337452.4
NIPA1	ENST00000437912.6	c.-48+12361_-48+12363dupGGC		intron_variant		1		ENSP00000393962.2
NIPA1	ENST00000561183.5	c.-48+426_-48+428dupGGC		intron_variant		1		ENSP00000453722.1
NIPA1	ENST00000560069.5	n.31+426_31+428dupGGC		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.000183 AC: 2 AN: 10952 Hom.: 0 AF XY: 0.000310 AC XY: 2 AN XY: 6444

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000443

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000485 AC: 45 AN: 926956 Hom.: 0 Cov.: 21 AF XY: 0.0000428 AC XY: 19 AN XY: 443684

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: 0.000122

Gnomad4 NFE exome AF: 0.0000525

Gnomad4 OTH exome AF: 0.0000306

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 6 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 27, 2024

- -

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: rs1555371601; hg19: chr15-23086397;