14-36516696-AG-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001079668.3(NKX2-1):c.*581delC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 232,788 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 0 hom. )

Consequence

NKX2-1
NM_001079668.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.02

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 -10 ACMG points.

BP6

Variant 14-36516696-AG-A is Benign according to our data. Variant chr14-36516696-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 313123.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00352 (536/152204) while in subpopulation AFR AF = 0.0124 (513/41516). AF 95% confidence interval is 0.0115. There are 4 homozygotes in GnomAd4. There are 258 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 536 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NKX2-1	NM_001079668.3 link	c.*581delC	3_prime_UTR_variant	Exon 3 of 3	ENST00000354822.7	NP_001073136.1	P43699-3
NKX2-1	NM_003317.4 link	c.*581delC	3_prime_UTR_variant	Exon 2 of 2		NP_003308.1	P43699-1
SFTA3	NR_161364.1 link	n.89+2771delC	intron_variant	Intron 1 of 4
SFTA3	NR_161365.1 link	n.89+2771delC	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.*581delC		3_prime_UTR_variant	Exon 3 of 3	1	NM_001079668.3	ENSP00000346879.6		P43699-3
SFTA3	ENST00000546983.2 link	n.373+2288delC		intron_variant	Intron 2 of 3	4		ENSP00000449302.2		F8VVG2

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

538

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.000893

AC:

AN:

80584

Hom.:

Cov.:

AF XY:

0.000808

AC XY:

AN XY:

37146

show subpopulations

African (AFR)

AF:

0.0125

AC:

AN:

3840

American (AMR)

AF:

0.000404

AC:

AN:

2476

Ashkenazi Jewish (ASJ)

AF:

0.00118

AC:

AN:

5064

East Asian (EAS)

AF:

0.00

AC:

AN:

11274

South Asian (SAS)

AF:

0.00

AC:

AN:

698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

478

Middle Eastern (MID)

AF:

0.00206

AC:

AN:

486

European-Non Finnish (NFE)

AF:

0.000101

AC:

AN:

49566

Other (OTH)

AF:

0.00164

AC:

AN:

6702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00352

AC:

536

AN:

152204

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

258

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0124

AC:

513

AN:

41516

American (AMR)

AF:

0.000981

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00372

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brain-lung-thyroid syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Benign hereditary chorea

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

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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14-36516696-AG-A

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