NM_001079668.3:c.*459_*460delTT

Variant names:

• chr14-36516817-CAA-C
• rs5807883
• NM_001079668.3:c.*459_*460delTT

Variant summary

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

The NM_001079668.3(NKX2-1):​c.*459_*460delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00639 in 216,296 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 0.0025 (3 hom., cov: 0)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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 eas. gnomad4 allele frequency = 0.00253 (360/142378) while in subpopulation EAS AF= 0.0313 (154/4918). AF 95% confidence interval is 0.0273. There are 3 homozygotes in gnomad4. There are 175 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 360 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX2-1	NM_001079668.3	c.*459_*460delTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000354822.7	NP_001073136.1
NKX2-1	NM_003317.4	c.*459_*460delTT		3_prime_UTR_variant	Exon 2 of 2		NP_003308.1
SFTA3	NR_161364.1	n.89+2649_89+2650delTT		intron_variant	Intron 1 of 4
SFTA3	NR_161365.1	n.89+2649_89+2650delTT		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822	c.*459_*460delTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_001079668.3	ENSP00000346879.6
SFTA3	ENST00000546983.2	n.373+2166_373+2167delTT		intron_variant	Intron 2 of 3	4		ENSP00000449302.2

Frequencies

GnomAD3 genomes AF: 0.00253 AC: 360 AN: 142320 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.00362

Gnomad FIN AF: 0.000682

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000214

Gnomad OTH AF: 0.00203

GnomAD4 exome AF: 0.0138 AC: 1023 AN: 73918 Hom.: 0 AF XY: 0.0134 AC XY: 458 AN XY: 34066

Gnomad4 AFR exome AF: 0.00794

Gnomad4 AMR exome AF: 0.0230

Gnomad4 ASJ exome AF: 0.00444

Gnomad4 EAS exome AF: 0.0509

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0349

Gnomad4 NFE exome AF: 0.00724

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.00253 AC: 360 AN: 142378 Hom.: 3 Cov.: 0 AF XY: 0.00254 AC XY: 175 AN XY: 68882

Gnomad4 AFR AF: 0.00390

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0313

Gnomad4 SAS AF: 0.00363

Gnomad4 FIN AF: 0.000682

Gnomad4 NFE AF: 0.000214

Gnomad4 OTH AF: 0.00201

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: rs5807883; hg19: chr14-36986022;