rs766062224

Variant names:

• chr20-63247727-G-A
• rs766062224
• NM_152864.4:c.322C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-63247727-G-A
• chr20-63247727-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152864.4(NKAIN4):​c.322C>T​(p.Arg108Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,494,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: NKAIN4 NM_152864.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

Genes affected

NKAIN4 (HGNC:16191): (sodium/potassium transporting ATPase interacting 4) NKAIN4 is a member of a family of mammalian proteins (see NKAIN1; MIM 612871) with similarity to Drosophila Nkain and interacts with the beta subunit of Na,K-ATPase (ATP1B1; MIM 182330) (Gorokhova et al., 2007 [PubMed 17606467]).[supplied by OMIM, Jun 2009]

LOC124904950 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3634867).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152864.4. 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
	NKAIN4	NM_152864.4	MANE Select	c.322C>T	p.Arg108Cys	missense	Exon 4 of 7	NP_690603.3
	NKAIN4	NM_001363747.1		c.136C>T	p.Arg46Cys	missense	Exon 4 of 7	NP_001350676.1	A6NNM2
	NKAIN4	NM_001363718.1		c.136C>T	p.Arg46Cys	missense	Exon 4 of 6	NP_001350647.1	J3JS66

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKAIN4	ENST00000370316.8	TSL:1 MANE Select	c.322C>T	p.Arg108Cys	missense	Exon 4 of 7	ENSP00000359340.3	Q8IVV8
	NKAIN4	ENST00000370317.3	TSL:5	c.112C>T	p.Arg38Cys	missense	Exon 2 of 6	ENSP00000359341.3	J9JIE8
	NKAIN4	ENST00000370307.6	TSL:5	c.136C>T	p.Arg46Cys	missense	Exon 4 of 7	ENSP00000359330.2	A6NNM2

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152234 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000881 AC: 10 AN: 113554 AF XY: 0.0000682

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000229

Gnomad NFE exome AF: 0.0000228

Gnomad OTH exome AF: 0.000309

GnomAD4 exome AF: 0.00000968 AC: 13 AN: 1342684 Hom.: 0 Cov.: 34 AF XY: 0.00000915 AC XY: 6 AN XY: 655806

African (AFR) AF: 0.0000335 AC: 1 AN: 29838

American (AMR) AF: 0.000216 AC: 6 AN: 27776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22000

East Asian (EAS) AF: 0.00 AC: 0 AN: 35032

South Asian (SAS) AF: 0.00 AC: 0 AN: 70060

European-Finnish (FIN) AF: 0.0000646 AC: 3 AN: 46464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5368

European-Non Finnish (NFE) AF: 0.00000190 AC: 2 AN: 1050652

Other (OTH) AF: 0.0000180 AC: 1 AN: 55494

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152234 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.7
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.046
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.049	D
Polyphen		0.99	D
Vest4		0.17
MutPred		0.50		Loss of MoRF binding (P = 0.0073)
MVP		0.25
MPC		0.034
ClinPred		0.81	D
GERP RS		-0.45
Varity_R		0.15
gMVP		0.16
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs766062224; hg19: chr20-61879079;