14-36517091-A-AGGGTGGGG

Variant names:

• chr14-36517091-A-AGGGTGGGG
• rs141117763
• NM_001079668.3:c.*186_*187insCCCCACCC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS2

The NM_001079668.3(NKX2-1):​c.*186_*187insCCCCACCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000057 in 876,710 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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]

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX2-1	NM_001079668.3	c.*186_*187insCCCCACCC		3_prime_UTR_variant	Exon 3 of 3	ENST00000354822.7	NP_001073136.1
NKX2-1	NM_003317.4	c.*186_*187insCCCCACCC		3_prime_UTR_variant	Exon 2 of 2		NP_003308.1
SFTA3	NR_161364.1	n.89+2376_89+2377insCCCCACCC		intron_variant	Intron 1 of 4
SFTA3	NR_161365.1	n.89+2376_89+2377insCCCCACCC		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822	c.*186_*187insCCCCACCC		3_prime_UTR_variant	Exon 3 of 3	1	NM_001079668.3	ENSP00000346879.6
SFTA3	ENST00000546983.2	n.373+1893_373+1894insCCCCACCC		intron_variant	Intron 2 of 3	4		ENSP00000449302.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000570 AC: 5 AN: 876710 Hom.: 0 Cov.: 12 AF XY: 0.00000464 AC XY: 2 AN XY: 430772

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000723

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

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;