rs200848675

Variant names:

• chr14-36517098-GAAAAA-G
• rs200848675
• NM_001079668.3:c.*175_*179delTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr14-36517098-GAAAAA-G
• chr14-36517098-GAAAAA-GA
• chr14-36517098-GAAAAA-GAA
• chr14-36517098-GAAAAA-GAAAA
• chr14-36517098-GAAAAA-GAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001079668.3(NKX2-1):​c.*175_*179delTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,163,426 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: NKX2-1 NM_001079668.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX2-1	NM_001079668.3	c.*175_*179delTTTTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000354822.7	NP_001073136.1
NKX2-1	NM_003317.4	c.*175_*179delTTTTT		3_prime_UTR_variant	Exon 2 of 2		NP_003308.1
SFTA3	NR_161364.1	n.89+2365_89+2369delTTTTT		intron_variant	Intron 1 of 4
SFTA3	NR_161365.1	n.89+2365_89+2369delTTTTT		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822.7	c.*175_*179delTTTTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_001079668.3	ENSP00000346879.6
SFTA3	ENST00000546983.2	n.373+1882_373+1886delTTTTT		intron_variant	Intron 2 of 3	4		ENSP00000449302.2

Frequencies

GnomAD3 genomes AF: 0.000146 AC: 22 AN: 151148 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000177

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000141 AC: 143 AN: 1012278 Hom.: 0 AF XY: 0.000140 AC XY: 69 AN XY: 493418

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21674

American (AMR) AF: 0.000156 AC: 2 AN: 12852

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 32 AN: 15762

East Asian (EAS) AF: 0.00 AC: 0 AN: 28048

South Asian (SAS) AF: 0.0000679 AC: 3 AN: 44194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2924

European-Non Finnish (NFE) AF: 0.000125 AC: 102 AN: 815146

Other (OTH) AF: 0.0000932 AC: 4 AN: 42932

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000146 AC: 22 AN: 151148 Hom.: 0 Cov.: 28 AF XY: 0.000136 AC XY: 10 AN XY: 73642

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41312

American (AMR) AF: 0.000264 AC: 4 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67740

Other (OTH) AF: 0.00 AC: 0 AN: 2080

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs200848675; hg19: chr14-36986303;