rs531550505

Variant names:

• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-A
• rs531550505
• NM_144599.5:c.27_47delGGCGGCGGCGGCGGCGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-A
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr15-22786677-AGCGGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_144599.5(NIPA1):​c.27_47delGGCGGCGGCGGCGGCGGCGGC​(p.Ala10_Ala16del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,071,500 control chromosomes in the GnomAD database, including 3 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 6)
  • Exomes 𝑓: 0.000046 (3 hom.)
• Consequence: NIPA1 NM_144599.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• Publications: 11 publications found

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]

NIPA1 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 6

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_144599.5
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144599.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA1	NM_144599.5	MANE Select	c.27_47delGGCGGCGGCGGCGGCGGCGGC	p.Ala10_Ala16del	disruptive_inframe_deletion	Exon 1 of 5	NP_653200.2
	NIPA1	NM_001142275.1		c.-48+435_-48+455delGGCGGCGGCGGCGGCGGCGGC		intron	N/A	NP_001135747.1	Q8TAY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA1	ENST00000337435.9	TSL:1 MANE Select	c.27_47delGGCGGCGGCGGCGGCGGCGGC	p.Ala10_Ala16del	disruptive_inframe_deletion	Exon 1 of 5	ENSP00000337452.4	Q7RTP0-1
	NIPA1	ENST00000437912.6	TSL:1	c.-48+12370_-48+12390delGGCGGCGGCGGCGGCGGCGGC		intron	N/A	ENSP00000393962.2	Q7RTP0-2
	NIPA1	ENST00000561183.5	TSL:1	c.-48+435_-48+455delGGCGGCGGCGGCGGCGGCGGC		intron	N/A	ENSP00000453722.1	Q7RTP0-2

Frequencies

GnomAD3 genomes AF: 0.0000344 AC: 5 AN: 145406 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000207

Gnomad SAS AF: 0.000638

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000347 AC: 7 AN: 20176 AF XY: 0.000474

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000464 AC: 43 AN: 926094 Hom.: 3 AF XY: 0.0000723 AC XY: 32 AN XY: 442826

African (AFR) AF: 0.00 AC: 0 AN: 17460

American (AMR) AF: 0.000171 AC: 1 AN: 5856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8166

East Asian (EAS) AF: 0.00 AC: 0 AN: 8916

South Asian (SAS) AF: 0.00110 AC: 24 AN: 21810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8024

Middle Eastern (MID) AF: 0.000381 AC: 1 AN: 2628

European-Non Finnish (NFE) AF: 0.0000207 AC: 17 AN: 820602

Other (OTH) AF: 0.00 AC: 0 AN: 32632

GnomAD4 genome AF: 0.0000344 AC: 5 AN: 145406 Hom.: 0 Cov.: 6 AF XY: 0.0000424 AC XY: 3 AN XY: 70686

African (AFR) AF: 0.00 AC: 0 AN: 40094

American (AMR) AF: 0.00 AC: 0 AN: 14774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.000207 AC: 1 AN: 4834

South Asian (SAS) AF: 0.000638 AC: 3 AN: 4704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65568

Other (OTH) AF: 0.00 AC: 0 AN: 2014

Alfa AF: 0.00 Hom.: 108

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hereditary spastic paraplegia 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs531550505; hg19: chr15-23086391;