Genetic Variant NM_001079668.3:c.*460dupT (chr14-36516817-C-CA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001079668.3(NKX2-1):c.*460dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.42 ( 12453 hom., cov: 0)

Exomes 𝑓: 0.35 ( 73 hom. )

Consequence

NKX2-1
NM_001079668.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: -1.44

Publications

1 publications found

Variant links:

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]

NKX2-1 links:

SFTA3 (HGNC:):

SFTA3 links:

SFTA3 (HGNC:18387): (surfactant associated 3) Involved in wound healing. Located in cytoplasm and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SFTA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NKX2-1	NM_001079668.3 link	c.*460dupT	3_prime_UTR_variant	Exon 3 of 3	ENST00000354822.7	NP_001073136.1	P43699-3
NKX2-1	NM_003317.4 link	c.*460dupT	3_prime_UTR_variant	Exon 2 of 2		NP_003308.1	P43699-1
SFTA3	NR_161364.1 link	n.89+2650dupT	intron_variant	Intron 1 of 4
SFTA3	NR_161365.1 link	n.89+2650dupT	intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822.7 link	c.*460dupT		3_prime_UTR_variant	Exon 3 of 3	1	NM_001079668.3	ENSP00000346879.6		P43699-3
SFTA3	ENST00000546983.2 link	n.373+2167dupT		intron_variant	Intron 2 of 3	4		ENSP00000449302.2		F8VVG2

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

59489

AN:

142150

Hom.:

12457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.384

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.414

GnomAD4 exome

AF:

0.346

AC:

25368

AN:

73350

Hom.:

Cov.:

AF XY:

0.347

AC XY:

11701

AN XY:

33746

show subpopulations

African (AFR)

AF:

0.287

AC:

1006

AN:

3510

American (AMR)

AF:

0.292

AC:

645

AN:

2210

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

1637

AN:

4656

East Asian (EAS)

AF:

0.395

AC:

4009

AN:

10158

South Asian (SAS)

AF:

0.305

AC:

208

AN:

682

European-Finnish (FIN)

AF:

0.314

AC:

AN:

Middle Eastern (MID)

AF:

0.328

AC:

149

AN:

454

European-Non Finnish (NFE)

AF:

0.343

AC:

15590

AN:

45460

Other (OTH)

AF:

0.342

AC:

2097

AN:

6134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.415

Heterozygous variant carriers

885

1770

2654

3539

4424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.418

AC:

59483

AN:

142206

Hom.:

12453

Cov.:

AF XY:

0.418

AC XY:

28728

AN XY:

68768

show subpopulations

African (AFR)

AF:

0.325

AC:

12251

AN:

37680

American (AMR)

AF:

0.383

AC:

5552

AN:

14478

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

1532

AN:

3342

East Asian (EAS)

AF:

0.603

AC:

2962

AN:

4916

South Asian (SAS)

AF:

0.420

AC:

1848

AN:

4400

European-Finnish (FIN)

AF:

0.431

AC:

3786

AN:

8792

Middle Eastern (MID)

AF:

0.404

AC:

109

AN:

270

European-Non Finnish (NFE)

AF:

0.461

AC:

30196

AN:

65462

Other (OTH)

AF:

0.413

AC:

822

AN:

1988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1591

3182

4773

6364

7955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.272

Hom.:

504

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brain-lung-thyroid syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Benign hereditary chorea

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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NM_001079668.3:c.*460dupT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over