14-36517091-A-AGGGTGG

Variant names:

• chr14-36517091-A-AGGGTGG
• rs141117763
• NM_001079668.3:c.*186_*187insCCACCC

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.*186_*187insCCACCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,022,566 control chromosomes in the GnomAD database, including 26,322 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3382 hom., cov: 28)
  • Exomes 𝑓: 0.22 (22940 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0890
• Publications: 1 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 14-36517091-A-AGGGTGG is Benign according to our data. Variant chr14-36517091-A-AGGGTGG is described in ClinVar as Benign. ClinVar VariationId is 1272844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 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.*186_*187insCCACCC		3_prime_UTR	Exon 3 of 3	NP_001073136.1	P43699-3
	NKX2-1	NM_003317.4		c.*186_*187insCCACCC		3_prime_UTR	Exon 2 of 2	NP_003308.1	P43699-1
	SFTA3	NR_161364.1		n.89+2376_89+2377insCCACCC		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.*186_*187insCCACCC		3_prime_UTR	Exon 3 of 3	ENSP00000346879.6	P43699-3
	NKX2-1	ENST00000498187.6	TSL:1	c.*186_*187insCCACCC		3_prime_UTR	Exon 2 of 2	ENSP00000429607.2	P43699-1
	SFTA3	ENST00000546983.2	TSL:4	n.373+1893_373+1894insCCACCC		intron	N/A	ENSP00000449302.2	F8VVG2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28406 AN: 149446 Hom.: 3384 Cov.: 28

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.220 AC: 192106 AN: 873038 Hom.: 22940 Cov.: 12 AF XY: 0.219 AC XY: 94145 AN XY: 428928

African (AFR) AF: 0.0359 AC: 714 AN: 19880

American (AMR) AF: 0.206 AC: 2573 AN: 12472

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 4067 AN: 14590

East Asian (EAS) AF: 0.102 AC: 2809 AN: 27674

South Asian (SAS) AF: 0.123 AC: 5047 AN: 41044

European-Finnish (FIN) AF: 0.197 AC: 5437 AN: 27640

Middle Eastern (MID) AF: 0.211 AC: 562 AN: 2660

European-Non Finnish (NFE) AF: 0.236 AC: 162745 AN: 688850

Other (OTH) AF: 0.213 AC: 8152 AN: 38228

GnomAD4 genome AF: 0.190 AC: 28403 AN: 149528 Hom.: 3382 Cov.: 28 AF XY: 0.190 AC XY: 13795 AN XY: 72782

African (AFR) AF: 0.0489 AC: 2006 AN: 40996

American (AMR) AF: 0.232 AC: 3477 AN: 15000

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1045 AN: 3450

East Asian (EAS) AF: 0.0857 AC: 438 AN: 5112

South Asian (SAS) AF: 0.142 AC: 677 AN: 4762

European-Finnish (FIN) AF: 0.221 AC: 2120 AN: 9604

Middle Eastern (MID) AF: 0.220 AC: 63 AN: 286

European-Non Finnish (NFE) AF: 0.264 AC: 17804 AN: 67352

Other (OTH) AF: 0.219 AC: 453 AN: 2068

Alfa AF: 0.0832 Hom.: 126

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		0.089
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: rs141117763; hg19: chr14-36986296; COSMIC: COSV61389859; COSMIC: COSV61389859;