chr14-36517060-C-CT

Variant names:

• chr14-36517060-C-CT
• rs71124756
• NM_001079668.3:c.*217dupA

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.*217dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 767,596 control chromosomes in the GnomAD database, including 24,439 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6267 hom., cov: 21)
  • Exomes 𝑓: 0.27 (18172 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.476
• Publications: 3 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:):

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 14-36517060-C-CT is Benign according to our data. Variant chr14-36517060-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1287959.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.404 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.*217dupA		3_prime_UTR	Exon 3 of 3	NP_001073136.1	P43699-3
	NKX2-1	NM_003317.4		c.*217dupA		3_prime_UTR	Exon 2 of 2	NP_003308.1	P43699-1
	SFTA3	NR_161364.1		n.89+2407dupA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-1	ENST00000354822.7	TSL:1 MANE Select	c.*217dupA		3_prime_UTR	Exon 3 of 3	ENSP00000346879.6	P43699-3
	NKX2-1	ENST00000498187.6	TSL:1	c.*217dupA		3_prime_UTR	Exon 2 of 2	ENSP00000429607.2	P43699-1
	SFTA3	ENST00000546983.2	TSL:4	n.373+1924dupA		intron	N/A	ENSP00000449302.2	F8VVG2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 39599 AN: 147790 Hom.: 6260 Cov.: 21

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.265 AC: 164336 AN: 619706 Hom.: 18172 Cov.: 10 AF XY: 0.267 AC XY: 82793 AN XY: 310382

African (AFR) AF: 0.0792 AC: 1333 AN: 16836

American (AMR) AF: 0.369 AC: 4690 AN: 12706

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 3823 AN: 12446

East Asian (EAS) AF: 0.276 AC: 7027 AN: 25442

South Asian (SAS) AF: 0.203 AC: 8028 AN: 39460

European-Finnish (FIN) AF: 0.263 AC: 6192 AN: 23544

Middle Eastern (MID) AF: 0.233 AC: 498 AN: 2134

European-Non Finnish (NFE) AF: 0.273 AC: 124876 AN: 457670

Other (OTH) AF: 0.267 AC: 7869 AN: 29468

GnomAD4 genome AF: 0.268 AC: 39612 AN: 147890 Hom.: 6267 Cov.: 21 AF XY: 0.271 AC XY: 19432 AN XY: 71712

African (AFR) AF: 0.103 AC: 4164 AN: 40606

American (AMR) AF: 0.413 AC: 6142 AN: 14876

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1217 AN: 3438

East Asian (EAS) AF: 0.275 AC: 1394 AN: 5066

South Asian (SAS) AF: 0.234 AC: 1090 AN: 4664

European-Finnish (FIN) AF: 0.287 AC: 2616 AN: 9106

Middle Eastern (MID) AF: 0.245 AC: 70 AN: 286

European-Non Finnish (NFE) AF: 0.328 AC: 21944 AN: 66902

Other (OTH) AF: 0.298 AC: 613 AN: 2058

Alfa AF: 0.104 Hom.: 200

Asia WGS AF: 0.258 AC: 897 AN: 3478

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		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs71124756; hg19: chr14-36986265; COSMIC: COSV61387327; COSMIC: COSV61387327;