NM_145285.3:c.358+610C>T

Variant names:

• chr10-99534099-C-T
• rs884144
• NM_145285.3:c.358+610C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NKX2-3	NM_145285.3	c.358+610C>T		intron_variant	Intron 1 of 1	ENST00000344586.9	NP_660328.2
NKX2-3	XM_011539370.2	c.358+610C>T		intron_variant	Intron 1 of 1		XP_011537672.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-3	ENST00000344586.9	c.358+610C>T		intron_variant	Intron 1 of 1	2	NM_145285.3	ENSP00000342828.7

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

African (AFR) AF: 0.125 AC: 5187 AN: 41536

American (AMR) AF: 0.117 AC: 1796 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3472

East Asian (EAS) AF: 0.0233 AC: 121 AN: 5188

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4824

European-Finnish (FIN) AF: 0.0630 AC: 669 AN: 10614

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9258 AN: 68022

Other (OTH) AF: 0.123 AC: 259 AN: 2114

Alfa AF: 0.132 Hom.: 3717

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
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs884144; hg19: chr10-101293856;