NM_152864.4:c.329G>T

Variant names:

• chr20-63247720-C-A
• rs76984019
• NM_152864.4:c.329G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152864.4(NKAIN4):​c.329G>T​(p.Arg110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,506,774 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R110H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0059 (6 hom., cov: 34)
  • Exomes 𝑓: 0.00062 (10 hom.)
• Consequence: NKAIN4 NM_152864.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070967674).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00593 (903/152342) while in subpopulation AFR AF = 0.0209 (867/41576). AF 95% confidence interval is 0.0197. There are 6 homozygotes in GnomAd4. There are 437 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.329G>T	p.Arg110Leu	missense	Exon 4 of 7	NP_690603.3
	NKAIN4	NM_001363747.1		c.143G>T	p.Arg48Leu	missense	Exon 4 of 7	NP_001350676.1	A6NNM2
	NKAIN4	NM_001363718.1		c.143G>T	p.Arg48Leu	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.329G>T	p.Arg110Leu	missense	Exon 4 of 7	ENSP00000359340.3	Q8IVV8
	NKAIN4	ENST00000370317.3	TSL:5	c.119G>T	p.Arg40Leu	missense	Exon 2 of 6	ENSP00000359341.3	J9JIE8
	NKAIN4	ENST00000370307.6	TSL:5	c.143G>T	p.Arg48Leu	missense	Exon 4 of 7	ENSP00000359330.2	A6NNM2

Frequencies

GnomAD3 genomes AF: 0.00593 AC: 902 AN: 152224 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.0209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00161 AC: 196 AN: 121466 AF XY: 0.00136

Gnomad AFR exome AF: 0.0212

Gnomad AMR exome AF: 0.000823

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000640

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.000624 AC: 845 AN: 1354432 Hom.: 10 Cov.: 34 AF XY: 0.000562 AC XY: 373 AN XY: 663232

African (AFR) AF: 0.0237 AC: 717 AN: 30226

American (AMR) AF: 0.00137 AC: 40 AN: 29242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22690

East Asian (EAS) AF: 0.00 AC: 0 AN: 35152

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 72112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46812

Middle Eastern (MID) AF: 0.000553 AC: 3 AN: 5422

European-Non Finnish (NFE) AF: 0.00000662 AC: 7 AN: 1056812

Other (OTH) AF: 0.00138 AC: 77 AN: 55964

GnomAD4 genome AF: 0.00593 AC: 903 AN: 152342 Hom.: 6 Cov.: 34 AF XY: 0.00587 AC XY: 437 AN XY: 74490

African (AFR) AF: 0.0209 AC: 867 AN: 41576

American (AMR) AF: 0.00170 AC: 26 AN: 15314

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00468 Hom.: 5

Bravo AF: 0.00660

ESP6500AA AF: 0.0169 AC: 66

ESP6500EA AF: 0.000406 AC: 3

ExAC AF: 0.00118 AC: 62

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.060
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.14	B
Vest4		0.29
MVP		0.16
MPC		0.0093
ClinPred		0.060	T
GERP RS		2.4
Varity_R		0.19
gMVP		0.24
Mutation Taster		=93/7	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: rs76984019; hg19: chr20-61879072; COSMIC: COSV99059104; COSMIC: COSV99059104;