14-36517091-A-AGGGTGG

Variant summary

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

The NM_001079668.3(NKX2-1):c.*186_*187insCCACCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,022,566 control chromosomes in the GnomAD database, including 26,322 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3382 hom., cov: 28)
  • Exomes 𝑓: 0.22 (22940 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0890

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 14-36517091-A-AGGGTGG is Benign according to our data. Variant chr14-36517091-A-AGGGTGG is described in ClinVar as [Benign]. Clinvar id is 1272844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKX2-1	NM_001079668.3	c.*186_*187insCCACCC		3_prime_UTR_variant	3/3	ENST00000354822.7
SFTA3	NR_161364.1	n.89+2376_89+2377insCCACCC		intron_variant, non_coding_transcript_variant
NKX2-1	NM_003317.4	c.*186_*187insCCACCC		3_prime_UTR_variant	2/2
SFTA3	NR_161365.1	n.89+2376_89+2377insCCACCC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX2-1	ENST00000354822.7	c.*186_*187insCCACCC		3_prime_UTR_variant	3/3	1	NM_001079668.3	P4
NKX2-1	ENST00000498187.6	c.*186_*187insCCACCC		3_prime_UTR_variant	2/2	1		A1
	ENST00000634305.1	n.322+68257_322+68258insTGGGGG		intron_variant, non_coding_transcript_variant		5
NKX2-1	ENST00000518149.5	c.*186_*187insCCACCC		3_prime_UTR_variant	3/3	5		A1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28406 AN: 149446 Hom.: 3384 Cov.: 28

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.220 AC: 192106 AN: 873038 Hom.: 22940 Cov.: 12 AF XY: 0.219 AC XY: 94145 AN XY: 428928

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.190 AC: 28403 AN: 149528 Hom.: 3382 Cov.: 28 AF XY: 0.190 AC XY: 13795 AN XY: 72782

Gnomad4 AFR AF: 0.0489

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.0857

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.219

Alfa AF: 0.0832 Hom.: 126

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

Nov 01, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs141117763; hg19: chr14-36986296;