chr1-24419637-C-T

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

2

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]

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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
NIPAL3NM_020448.5 linkc.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
NIPAL3ENST00000374399.9 linkc.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:
80
AN:
152240
Hom.:
1
Cov.:
32
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.:
2
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.:
16
Cov.:
30
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:
80
AN:
152358
Hom.:
1
Cov.:
32
AF XY:
0.000631
AC XY:
47
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.:
0
Bravo
AF:
0.000737
Asia WGS
AF:
0.00375
AC:
13
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.

Other links and lift over

dbSNP: rs2294521; hg19: chr1-24746127; COSMIC: COSV50232115; COSMIC: COSV50232115; API