chr20-63247655-G-C

Position:

• chr20-63247655-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152864.4(NKAIN4):​c.394C>G​(p.Leu132Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: NKAIN4 NM_152864.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.915

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14923918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKAIN4	NM_152864.4	c.394C>G	p.Leu132Val	missense_variant	4/7	ENST00000370316.8	NP_690603.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKAIN4	ENST00000370316.8	c.394C>G	p.Leu132Val	missense_variant	4/7	1	NM_152864.4	ENSP00000359340.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.394C>G (p.L132V) alteration is located in exon 4 (coding exon 4) of the NKAIN4 gene. This alteration results from a C to G substitution at nucleotide position 394, causing the leucine (L) at amino acid position 132 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.7
DANN	Benign	0.62
DEOGEN2	Benign	0.0013	.;T;.;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.57	T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;L;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.39	N;N;N;N
REVEL	Benign	0.029
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.30, 0.13	.;B;B;.
Vest4		0.086
MutPred		0.39		.;Gain of disorder (P = 0.2359);.;.;
MVP		0.16
MPC		0.0090
ClinPred		0.14	T
GERP RS		-2.6
Varity_R		0.032
gMVP		0.073

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-61879007;