14-36516817-C-CA

Position:

• chr14-36516817-C-CA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001079668.3(NKX2-1):​c.*460dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.42 (12453 hom., cov: 0)
  • Exomes 𝑓: 0.35 (73 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -1.44

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:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKX2-1	NM_001079668.3	c.*460dupT		3_prime_UTR_variant	3/3	ENST00000354822.7	NP_001073136.1
NKX2-1	NM_003317.4	c.*460dupT		3_prime_UTR_variant	2/2		NP_003308.1
SFTA3	NR_161364.1	n.89+2650dupT		intron_variant
SFTA3	NR_161365.1	n.89+2650dupT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822	c.*460dupT		3_prime_UTR_variant	3/3	1	NM_001079668.3	ENSP00000346879.6
SFTA3	ENST00000546983.2	n.373+2167dupT		intron_variant		4		ENSP00000449302.2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 59489 AN: 142150 Hom.: 12457 Cov.: 0

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.346 AC: 25368 AN: 73350 Hom.: 73 Cov.: 0 AF XY: 0.347 AC XY: 11701 AN XY: 33746

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.395

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.418 AC: 59483 AN: 142206 Hom.: 12453 Cov.: 0 AF XY: 0.418 AC XY: 28728 AN XY: 68768

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.413

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Brain-lung-thyroid syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Benign hereditary chorea Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs5807883; hg19: chr14-36986022;