14-36519723-AAGAG-AAGAGAG

Variant names:

• chr14-36519726-A-AGA
• NM_001079668.3:c.77+325_77+326dupTC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001079668.3(NKX2-1):​c.77+325_77+326dupTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NKX2-1 NM_001079668.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 0 publications found

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:):

NKX2-1-AS1 (HGNC:40585): (NKX2-1 antisense RNA 1)

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079668.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-1	NM_001079668.3	MANE Select	c.77+325_77+326dupTC		intron	N/A	NP_001073136.1	P43699-3
	NKX2-1-AS1	NR_103710.1		n.402+59_402+60dupAG		intron	N/A
	NKX2-1	NM_003317.4		c.-371_-370dupTC		upstream_gene	N/A	NP_003308.1	P43699-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-1	ENST00000354822.7	TSL:1 MANE Select	c.77+326_77+327insTC		intron	N/A	ENSP00000346879.6	P43699-3
	NKX2-1	ENST00000522719.4	TSL:1	c.-158-115_-158-114insTC		intron	N/A	ENSP00000429519.4	P43699-1
	SFTA3	ENST00000546983.2	TSL:4	n.-13-357_-13-356insTC		intron	N/A	ENSP00000449302.2	F8VVG2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-36988931;