20-63247601-T-C

Position:

• chr20-63247601-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152864.4(NKAIN4):​c.448A>G​(p.Ser150Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 3.87

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKAIN4	NM_152864.4	c.448A>G	p.Ser150Gly	missense_variant	4/7	ENST00000370316.8
LOC124904950	XM_047440633.1	c.*1621T>C		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKAIN4	ENST00000370316.8	c.448A>G	p.Ser150Gly	missense_variant	4/7	1	NM_152864.4	P1

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

Feb 23, 2023

The c.448A>G (p.S150G) alteration is located in exon 4 (coding exon 4) of the NKAIN4 gene. This alteration results from a A to G substitution at nucleotide position 448, causing the serine (S) at amino acid position 150 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	0.0029	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.91	D;D;D;D
MetaSVM	Benign	-0.67	T
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0060	D;D;D;D
Sift4G	Uncertain	0.021	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.58
MutPred		0.83		.;Gain of relative solvent accessibility (P = 0.09);.;.;
MVP		0.32
MPC		0.045
ClinPred		0.94	D
GERP RS		3.5
Varity_R		0.49
gMVP		0.22

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: chr20-61878953;