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

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001079668.3(NKX2-1):​c.77+328_77+329dupCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,443,664 control chromosomes in the GnomAD database, including 2,347 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (650 hom., cov: 31)
  • Exomes 𝑓: 0.10 (1697 hom.)
• Consequence: NKX2-1 NM_001079668.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.683
• Publications: 4 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 14-36519723-A-AAG is Benign according to our data. Variant chr14-36519723-A-AAG is described in ClinVar as Benign. ClinVar VariationId is 1296646.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

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+328_77+329dupCT		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.-368_-367dupCT		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+329_77+330insCT		intron	N/A	ENSP00000346879.6	P43699-3
	NKX2-1	ENST00000522719.4	TSL:1	c.-158-112_-158-111insCT		intron	N/A	ENSP00000429519.4	P43699-1
	SFTA3	ENST00000546983.2	TSL:4	n.-13-354_-13-353insCT		intron	N/A	ENSP00000449302.2	F8VVG2

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12668 AN: 151054 Hom.: 650 Cov.: 31

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.000970

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.103 AC: 133458 AN: 1292502 Hom.: 1697 Cov.: 28 AF XY: 0.103 AC XY: 65451 AN XY: 633982

African (AFR) AF: 0.0220 AC: 645 AN: 29356

American (AMR) AF: 0.0608 AC: 1939 AN: 31908

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3036 AN: 22558

East Asian (EAS) AF: 0.000571 AC: 18 AN: 31504

South Asian (SAS) AF: 0.0917 AC: 6637 AN: 72402

European-Finnish (FIN) AF: 0.0924 AC: 2706 AN: 29278

Middle Eastern (MID) AF: 0.186 AC: 981 AN: 5286

European-Non Finnish (NFE) AF: 0.110 AC: 112035 AN: 1016684

Other (OTH) AF: 0.102 AC: 5461 AN: 53526

GnomAD4 genome AF: 0.0838 AC: 12668 AN: 151162 Hom.: 650 Cov.: 31 AF XY: 0.0831 AC XY: 6135 AN XY: 73842

African (AFR) AF: 0.0244 AC: 1009 AN: 41356

American (AMR) AF: 0.0892 AC: 1354 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3460

East Asian (EAS) AF: 0.000973 AC: 5 AN: 5140

South Asian (SAS) AF: 0.0862 AC: 414 AN: 4800

European-Finnish (FIN) AF: 0.0984 AC: 1011 AN: 10274

Middle Eastern (MID) AF: 0.205 AC: 59 AN: 288

European-Non Finnish (NFE) AF: 0.118 AC: 7991 AN: 67658

Other (OTH) AF: 0.100 AC: 210 AN: 2094

Alfa AF: 0.0305 Hom.: 34

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs149047715; hg19: chr14-36988928; COSMIC: COSV61387841; COSMIC: COSV61387841;