14-36517060-C-CT

Position:

• chr14-36517060-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001079668.3(NKX2-1):​c.*217_*218insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 767,596 control chromosomes in the GnomAD database, including 24,439 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6267 hom., cov: 21)
  • Exomes 𝑓: 0.27 (18172 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.476

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-36517060-C-CT is Benign according to our data. Variant chr14-36517060-C-CT is described in ClinVar as [Benign]. Clinvar id is 1287959.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKX2-1	NM_001079668.3	c.*217_*218insA		3_prime_UTR_variant	3/3	ENST00000354822.7
SFTA3	NR_161364.1	n.89+2407_89+2408insA		intron_variant, non_coding_transcript_variant
NKX2-1	NM_003317.4	c.*217_*218insA		3_prime_UTR_variant	2/2
SFTA3	NR_161365.1	n.89+2407_89+2408insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX2-1	ENST00000354822.7	c.*217_*218insA		3_prime_UTR_variant	3/3	1	NM_001079668.3	P4
NKX2-1	ENST00000498187.6	c.*217_*218insA		3_prime_UTR_variant	2/2	1		A1
	ENST00000634305.1	n.322+68230dup		intron_variant, non_coding_transcript_variant		5
NKX2-1	ENST00000518149.5	c.*217_*218insA		3_prime_UTR_variant	3/3	5		A1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 39599 AN: 147790 Hom.: 6260 Cov.: 21

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.265 AC: 164336 AN: 619706 Hom.: 18172 Cov.: 10 AF XY: 0.267 AC XY: 82793 AN XY: 310382

Gnomad4 AFR exome AF: 0.0792

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.268 AC: 39612 AN: 147890 Hom.: 6267 Cov.: 21 AF XY: 0.271 AC XY: 19432 AN XY: 71712

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.298

Alfa AF: 0.104 Hom.: 200

Asia WGS AF: 0.258 AC: 897 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2018

- -

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: rs71124756; hg19: chr14-36986265;