rs888208

chr10-99536106-A-G

Variant summary

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

The NM_145285.3(NKX2-3):c.*385A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 228,802 control chromosomes in the GnomAD database, including 8,356 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 0.25 (5497 hom., cov: 33)
  • Exomes 𝑓: 0.25 (2859 hom.)
• Consequence: NKX2-3 NM_145285.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

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 (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKX2-3	NM_145285.3	c.*385A>G		3_prime_UTR_variant	2/2	ENST00000344586.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX2-3	ENST00000344586.9	c.*385A>G		3_prime_UTR_variant	2/2	2	NM_145285.3	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38279 AN: 152146 Hom.: 5494 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.246 AC: 18808 AN: 76538 Hom.: 2859 Cov.: 0 AF XY: 0.238 AC XY: 9415 AN XY: 39550

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.262

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.251 AC: 38288 AN: 152264 Hom.: 5497 Cov.: 33 AF XY: 0.257 AC XY: 19165 AN XY: 74438

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.249

Alfa AF: 0.270 Hom.: 4222

Bravo AF: 0.240

Asia WGS AF: 0.292 AC: 1017 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	3.5
Dann	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs888208; hg19: chr10-101295863; COSMIC: COSV60728688; COSMIC: COSV60728688;