8-62249126-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001304533.3(NKAIN3):c.53T>C(p.Leu18Ser) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NKAIN3 NM_001304533.3 missense, splice_region
• Scores: Splicing: ADA: 0.9026
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.24

Genes affected

NKAIN3 (HGNC:26829): (sodium/potassium transporting ATPase interacting 3) NKAIN3 is a member of a family of mammalian proteins (see NKAIN1; MIM 612871) with similarity to Drosophila Nkain (Gorokhova et al., 2007 [PubMed 17606467]).[supplied by OMIM, Jun 2009]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKAIN3	NM_001304533.3	c.53T>C	p.Leu18Ser	missense_variant, splice_region_variant	1/7	ENST00000623646.3
LOC124901952	XR_007060932.1	n.9273+331A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKAIN3	ENST00000623646.3	c.53T>C	p.Leu18Ser	missense_variant, splice_region_variant	1/7		NM_001304533.3	P1
	ENST00000649904.1	n.423+331A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1384396 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 683218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jul 19, 2023

The c.53T>C (p.L18S) alteration is located in exon 1 (coding exon 1) of the NKAIN3 gene. This alteration results from a T to C substitution at nucleotide position 53, causing the leucine (L) at amino acid position 18 to be replaced by a serine (S). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
Cadd	Pathogenic	29
Dann	Uncertain	1.0
DEOGEN2	Benign	0.040	T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.68	P;.
Vest4		0.75
MutPred		0.77		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);
MVP		0.32
MPC		0.73
ClinPred		0.95	D
GERP RS		4.4
Varity_R		0.40
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.90
dbscSNV1_RF	Pathogenic	0.83
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: chr8-63161685;