10-99536106-A-G

Variant names:

• chr10-99536106-A-G
• rs888208
• NM_145285.3:c.*385A>G

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.*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
• Publications: 17 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 (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145285.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-3	NM_145285.3	MANE Select	c.*385A>G		3_prime_UTR	Exon 2 of 2	NP_660328.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-3	ENST00000344586.9	TSL:2 MANE Select	c.*385A>G		3_prime_UTR	Exon 2 of 2	ENSP00000342828.7

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

African (AFR) AF: 0.112 AC: 204 AN: 1822

American (AMR) AF: 0.262 AC: 856 AN: 3264

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 453 AN: 2558

East Asian (EAS) AF: 0.411 AC: 1455 AN: 3544

South Asian (SAS) AF: 0.160 AC: 1116 AN: 6988

European-Finnish (FIN) AF: 0.340 AC: 1590 AN: 4678

Middle Eastern (MID) AF: 0.173 AC: 68 AN: 392

European-Non Finnish (NFE) AF: 0.246 AC: 11942 AN: 48514

Other (OTH) AF: 0.235 AC: 1124 AN: 4778

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

African (AFR) AF: 0.129 AC: 5357 AN: 41590

American (AMR) AF: 0.310 AC: 4747 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2250 AN: 5162

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4830

European-Finnish (FIN) AF: 0.380 AC: 4026 AN: 10592

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19322 AN: 68010

Other (OTH) AF: 0.249 AC: 525 AN: 2112

Alfa AF: 0.270 Hom.: 4954

Bravo AF: 0.240

Asia WGS AF: 0.292 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.54
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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