rs884144

Positions:

• chr10-99534099-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145285.3(NKX2-3):​c.358+610C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,268 control chromosomes in the GnomAD database, including 1,369 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1369 hom., cov: 33)
• Consequence: NKX2-3 NM_145285.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469

Genes affected

NKX2-3 (HGNC:7836): (NK2 homeobox 3) This gene encodes a homeodomain-containing transcription factor. The encoded protein is a member of the NKX family of homeodomain transcription factors. Studies of similar proteins in mouse and rat have indicated a potential role in cellular differentiation.[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKX2-3	NM_145285.3	c.358+610C>T		intron_variant		ENST00000344586.9	NP_660328.2
NKX2-3	XM_011539370.2	c.358+610C>T		intron_variant			XP_011537672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKX2-3	ENST00000344586.9	c.358+610C>T		intron_variant		2	NM_145285.3	ENSP00000342828	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19284 AN: 152150 Hom.: 1371 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19287 AN: 152268 Hom.: 1369 Cov.: 33 AF XY: 0.124 AC XY: 9220 AN XY: 74448

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0630

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.123

Alfa AF: 0.134 Hom.: 1452

Bravo AF: 0.127

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs884144; hg19: chr10-101293856;