6-124283055-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001040214.3(NKAIN2):c.105A>G(p.Ala35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 1,612,806 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (114 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (142 hom.)
• Consequence: NKAIN2 NM_001040214.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.27

Genes affected

NKAIN2 (HGNC:16443): (sodium/potassium transporting ATPase interacting 2) This gene encodes a transmembrane protein that interacts with the beta subunit of a sodium/potassium-transporting ATPase. A chromosomal translocation involving this gene is a cause of lymphoma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-124283055-A-G is Benign according to our data. Variant chr6-124283055-A-G is described in ClinVar as [Benign]. Clinvar id is 776152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKAIN2	NM_001040214.3	c.105A>G	p.Ala35=	synonymous_variant	2/7	ENST00000368417.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKAIN2	ENST00000368417.6	c.105A>G	p.Ala35=	synonymous_variant	2/7	5	NM_001040214.3	P1
NKAIN2	ENST00000368416.5	c.105A>G	p.Ala35=	synonymous_variant	2/4	1
NKAIN2	ENST00000476571.1	n.229A>G		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3404 AN: 152084 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00678 AC: 1705 AN: 251364 Hom.: 51 AF XY: 0.00505 AC XY: 686 AN XY: 135854

Gnomad AFR exome AF: 0.0747

Gnomad AMR exome AF: 0.00578

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00128

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00319 AC: 4663 AN: 1460604 Hom.: 142 Cov.: 29 AF XY: 0.00286 AC XY: 2079 AN XY: 726736

Gnomad4 AFR exome AF: 0.0811

Gnomad4 AMR exome AF: 0.00581

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000805

Gnomad4 OTH exome AF: 0.00698

GnomAD4 genome AF: 0.0225 AC: 3419 AN: 152202 Hom.: 114 Cov.: 32 AF XY: 0.0213 AC XY: 1584 AN XY: 74420

Gnomad4 AFR AF: 0.0750

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000765

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0110 Hom.: 21

Bravo AF: 0.0258

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00154

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	9.8
Dann	Benign	0.79

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: rs34368457; hg19: chr6-124604201;