14-36517067-T-TA

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001079668.3(NKX2-1):c.*210dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00778 in 873,584 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0065 ( 6 hom., cov: 29)

Exomes 𝑓: 0.0080 ( 13 hom. )

Consequence

NKX2-1
NM_001079668.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.620

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 -9 ACMG points.

BP6

Variant 14-36517067-T-TA is Benign according to our data. Variant chr14-36517067-T-TA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 313132.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00648 (938/144750) while in subpopulation NFE AF = 0.0104 (677/65206). AF 95% confidence interval is 0.00973. There are 6 homozygotes in GnomAd4. There are 429 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High AC in GnomAd4 at 938 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NKX2-1	NM_001079668.3 link	c.*210dupT	3_prime_UTR_variant	Exon 3 of 3	ENST00000354822.7	NP_001073136.1	P43699-3
NKX2-1	NM_003317.4 link	c.*210dupT	3_prime_UTR_variant	Exon 2 of 2		NP_003308.1	P43699-1
SFTA3	NR_161364.1 link	n.89+2400dupT	intron_variant	Intron 1 of 4
SFTA3	NR_161365.1 link	n.89+2400dupT	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.*210dupT		3_prime_UTR_variant	Exon 3 of 3	1	NM_001079668.3	ENSP00000346879.6		P43699-3
SFTA3	ENST00000546983.2 link	n.373+1917dupT		intron_variant	Intron 2 of 3	4		ENSP00000449302.2		F8VVG2

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

939

AN:

144634

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00708

Gnomad ASJ

AF:

0.000301

Gnomad EAS

AF:

0.00595

Gnomad SAS

AF:

0.00131

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00342

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00462

GnomAD4 exome

AF:

0.00804

AC:

5860

AN:

728834

Hom.:

Cov.:

AF XY:

0.00780

AC XY:

2827

AN XY:

362248

show subpopulations

African (AFR)

AF:

0.0117

AC:

189

AN:

16208

American (AMR)

AF:

0.00819

AC:

110

AN:

13430

Ashkenazi Jewish (ASJ)

AF:

0.00280

AC:

AN:

13232

East Asian (EAS)

AF:

0.0126

AC:

340

AN:

26964

South Asian (SAS)

AF:

0.00112

AC:

AN:

43860

European-Finnish (FIN)

AF:

0.00252

AC:

AN:

24996

Middle Eastern (MID)

AF:

0.00299

AC:

AN:

2338

European-Non Finnish (NFE)

AF:

0.00861

AC:

4777

AN:

554646

Other (OTH)

AF:

0.00869

AC:

288

AN:

33160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.403

Heterozygous variant carriers

204

409

613

818

1022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00648

AC:

938

AN:

144750

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

429

AN XY:

70300

show subpopulations

African (AFR)

AF:

0.00240

AC:

AN:

40384

American (AMR)

AF:

0.00707

AC:

100

AN:

14140

Ashkenazi Jewish (ASJ)

AF:

0.000301

AC:

AN:

3324

East Asian (EAS)

AF:

0.00596

AC:

AN:

5034

South Asian (SAS)

AF:

0.00132

AC:

AN:

4562

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

8996

Middle Eastern (MID)

AF:

0.00368

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.0104

AC:

677

AN:

65206

Other (OTH)

AF:

0.00457

AC:

AN:

1968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000928

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

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

- -

not provided

Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NKX2-1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.62

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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14-36517067-T-TA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over