NM_152864.4:c.311G>C

Variant names:

• chr20-63247738-C-G
• rs927666296
• NM_152864.4:c.311G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152864.4(NKAIN4):​c.311G>C​(p.Arg104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,334,586 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R104H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: NKAIN4 NM_152864.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.311G>C	p.Arg104Pro	missense	Exon 4 of 7	NP_690603.3
	NKAIN4	NM_001363747.1		c.125G>C	p.Arg42Pro	missense	Exon 4 of 7	NP_001350676.1	A6NNM2
	NKAIN4	NM_001363718.1		c.125G>C	p.Arg42Pro	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.311G>C	p.Arg104Pro	missense	Exon 4 of 7	ENSP00000359340.3	Q8IVV8
	NKAIN4	ENST00000370317.3	TSL:5	c.101G>C	p.Arg34Pro	missense	Exon 2 of 6	ENSP00000359341.3	J9JIE8
	NKAIN4	ENST00000370307.6	TSL:5	c.125G>C	p.Arg42Pro	missense	Exon 4 of 7	ENSP00000359330.2	A6NNM2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1334586 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 650622

African (AFR) AF: 0.00 AC: 0 AN: 29702

American (AMR) AF: 0.00 AC: 0 AN: 27234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21452

East Asian (EAS) AF: 0.00 AC: 0 AN: 34956

South Asian (SAS) AF: 0.00 AC: 0 AN: 68392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5294

European-Non Finnish (NFE) AF: 9.56e-7 AC: 1 AN: 1046296

Other (OTH) AF: 0.00 AC: 0 AN: 55188

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.76
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.17
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.31
MutPred		0.75		Loss of MoRF binding (P = 0.0034)
MVP		0.18
MPC		0.041
ClinPred		0.99	D
GERP RS		-2.0
Varity_R		0.63
gMVP		0.46
Mutation Taster		=77/23	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: rs927666296; hg19: chr20-61879090;