Genetic Variant NIPAL3:p.Tyr30Tyr (chr1-24419637-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_020448.5(NIPAL3):c.90C>T(p.Tyr30Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000801 in 1,613,648 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 16 hom. )

Consequence

NIPAL3
NM_020448.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0870

Variant links:

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]

NIPAL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 1-24419637-C-T is Benign according to our data. Variant chr1-24419637-C-T is described in ClinVar as [Benign]. Clinvar id is 3048167.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.087 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00083 (1213/1461290) while in subpopulation EAS AF= 0.0263 (1042/39688). AF 95% confidence interval is 0.0249. There are 16 homozygotes in gnomad4_exome. There are 584 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPAL3	NM_020448.5 link	c.90C>T	p.Tyr30Tyr	synonymous_variant	Exon 2 of 12	ENST00000374399.9	NP_065181.1	Q6P499-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPAL3	ENST00000374399.9 link	c.90C>T	p.Tyr30Tyr	synonymous_variant	Exon 2 of 12	1	NM_020448.5	ENSP00000363520.4		Q6P499-1

Frequencies

GnomAD3 genomes

AF:

0.000525

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00155

AC:

385

AN:

247890

Hom.:

AF XY:

0.00145

AC XY:

195

AN XY:

134300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0179

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.000830

AC:

1213

AN:

1461290

Hom.:

Cov.:

AF XY:

0.000803

AC XY:

584

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0263

Gnomad4 SAS exome

AF:

0.000221

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.0000900

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000525

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0135

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.000737

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NIPAL3-related disorder

Benign:1

Nov 16, 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

-0.53

CADD

Benign

9.6

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over