NM_001079668.3:c.77+328_77+329delCT

Variant names:

• chr14-36519723-AAG-A
• rs149047715
• NM_001079668.3:c.77+328_77+329delCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001079668.3(NKX2-1):​c.77+328_77+329delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 1,263,186 control chromosomes in the GnomAD database, including 30 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 31)
  • Exomes 𝑓: 0.026 (26 hom.)
• Consequence: NKX2-1 NM_001079668.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00335 (505/150960) while in subpopulation NFE AF= 0.00629 (425/67590). AF 95% confidence interval is 0.00579. There are 4 homozygotes in gnomad4. There are 207 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 505 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX2-1	NM_001079668.3	c.77+328_77+329delCT		intron_variant	Intron 1 of 2	ENST00000354822.7	NP_001073136.1
NKX2-1-AS1	NR_103710.1	n.402+59_402+60delAG		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822.7	c.77+328_77+329delCT		intron_variant	Intron 1 of 2	1	NM_001079668.3	ENSP00000346879.6
SFTA3	ENST00000546983.2	n.-13-355_-13-354delCT		intron_variant	Intron 1 of 3	4		ENSP00000449302.2

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 507 AN: 150854 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000294

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.00386

GnomAD4 exome AF: 0.0262 AC: 29182 AN: 1112226 Hom.: 26 AF XY: 0.0275 AC XY: 14959 AN XY: 544648

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.0430

Gnomad4 ASJ exome AF: 0.0274

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.0348

Gnomad4 FIN exome AF: 0.0467

Gnomad4 NFE exome AF: 0.0240

Gnomad4 OTH exome AF: 0.0275

GnomAD4 genome AF: 0.00335 AC: 505 AN: 150960 Hom.: 4 Cov.: 31 AF XY: 0.00281 AC XY: 207 AN XY: 73720

Gnomad4 AFR AF: 0.00119

Gnomad4 AMR AF: 0.00119

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.000294

Gnomad4 NFE AF: 0.00629

Gnomad4 OTH AF: 0.00382

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: rs149047715; hg19: chr14-36988928;