rs886050480

Variant names:

• chr14-36517067-TA-T
• rs886050480
• NM_001079668.3:c.*210delT

Your query was ambiguous. Multiple possible variants found:

• chr14-36517067-TA-T
• chr14-36517067-TA-TAA
• chr14-36517067-TA-TAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001079668.3(NKX2-1):​c.*210delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 869,976 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00046 (2 hom., cov: 29)
  • Exomes 𝑓: 0.0023 (1 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620

Genes affected

NKX2-1 (HGNC:11825): (NK2 homeobox 1) This gene encodes a protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TTF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Feb 2014]

SFTA3 (HGNC:):

SFTA3 (HGNC:18387): (surfactant associated 3) Involved in wound healing. Located in cytoplasm and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000463 (67/144762) while in subpopulation AFR AF= 0.00116 (47/40384). AF 95% confidence interval is 0.000899. There are 2 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX2-1	NM_001079668.3	c.*210delT		3_prime_UTR_variant	Exon 3 of 3	ENST00000354822.7	NP_001073136.1
NKX2-1	NM_003317.4	c.*210delT		3_prime_UTR_variant	Exon 2 of 2		NP_003308.1
SFTA3	NR_161364.1	n.89+2400delT		intron_variant	Intron 1 of 4
SFTA3	NR_161365.1	n.89+2400delT		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822	c.*210delT		3_prime_UTR_variant	Exon 3 of 3	1	NM_001079668.3	ENSP00000346879.6
SFTA3	ENST00000546983.2	n.373+1917delT		intron_variant	Intron 2 of 3	4		ENSP00000449302.2

Frequencies

GnomAD3 genomes AF: 0.000429 AC: 62 AN: 144646 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000425

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000438

Gnomad FIN AF: 0.000222

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000138

Gnomad OTH AF: 0.000513

GnomAD4 exome AF: 0.00227 AC: 1645 AN: 725214 Hom.: 1 Cov.: 10 AF XY: 0.00221 AC XY: 798 AN XY: 360436

Gnomad4 AFR exome AF: 0.00723

Gnomad4 AMR exome AF: 0.00254

Gnomad4 ASJ exome AF: 0.00174

Gnomad4 EAS exome AF: 0.00119

Gnomad4 SAS exome AF: 0.00310

Gnomad4 FIN exome AF: 0.00157

Gnomad4 NFE exome AF: 0.00215

Gnomad4 OTH exome AF: 0.00221

GnomAD4 genome AF: 0.000463 AC: 67 AN: 144762 Hom.: 2 Cov.: 29 AF XY: 0.000569 AC XY: 40 AN XY: 70310

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.000424

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000438

Gnomad4 FIN AF: 0.000222

Gnomad4 NFE AF: 0.000138

Gnomad4 OTH AF: 0.000508

Alfa AF: 0.000124 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs886050480; hg19: chr14-36986272;