1-24415834-C-T

Variant names:

• chr1-24415834-C-T
• rs139905565
• NM_020448.5:c.-328C>T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_020448.5(NIPAL3):​c.-328C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 985,388 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0042 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (4 hom.)
• Consequence: NIPAL3 NM_020448.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.506

Genes affected

NIPAL3 (HGNC:25233): (NIPA like domain containing 3) Predicted to enable magnesium ion transmembrane transporter activity. Predicted to be involved in magnesium ion transport. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

STPG1 (HGNC:28070): (sperm tail PG-rich repeat containing 1) Involved in positive regulation of apoptotic process and positive regulation of mitochondrial membrane permeability involved in apoptotic process. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 1-24415834-C-T is Benign according to our data. Variant chr1-24415834-C-T is described in ClinVar as [Benign]. Clinvar id is 3049381.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPAL3	NM_020448.5	c.-328C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	ENST00000374399.9	NP_065181.1
NIPAL3	NM_020448.5	c.-328C>T		5_prime_UTR_variant	Exon 1 of 12	ENST00000374399.9	NP_065181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPAL3	ENST00000374399	c.-328C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	1	NM_020448.5	ENSP00000363520.4
NIPAL3	ENST00000374399	c.-328C>T		5_prime_UTR_variant	Exon 1 of 12	1	NM_020448.5	ENSP00000363520.4

Frequencies

GnomAD3 genomes AF: 0.00415 AC: 632 AN: 152148 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000681 AC: 567 AN: 833122 Hom.: 4 Cov.: 29 AF XY: 0.000717 AC XY: 276 AN XY: 384738

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00854

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000182

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000301

Gnomad4 OTH exome AF: 0.00176

GnomAD4 genome AF: 0.00416 AC: 633 AN: 152266 Hom.: 2 Cov.: 32 AF XY: 0.00404 AC XY: 301 AN XY: 74428

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00281 Hom.: 0

Bravo AF: 0.00510

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NIPAL3-related disorder Benign:1

Jul 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.93

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: rs139905565; hg19: chr1-24742324;