rs538476099

Variant names:

• chr12-120978597-AGGGTTGG-A
• rs538476099
• NM_000545.8:c.-160_-154delTGGGGGT

Your query was ambiguous. Multiple possible variants found:

• chr12-120978597-AGGGTTGG-A
• chr12-120978597-AGGGTTGG-AGGGTTGGGGGTTGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000545.8(HNF1A):​c.-160_-154delTGGGGGT variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000752 in 664,828 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: HNF1A NM_000545.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74
• Publications: 1 publications found

Genes affected

HNF1A (HGNC:11621): (HNF1 homeobox A) The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

HNF1A-AS1 (HGNC:26785): (HNF1A antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1A	NM_000545.8	c.-160_-154delTGGGGGT		5_prime_UTR_variant	Exon 1 of 10	ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2	c.-160_-154delTGGGGGT		5_prime_UTR_variant	Exon 1 of 10		NP_001293108.2
HNF1A	NM_001406915.1	c.-160_-154delTGGGGGT		5_prime_UTR_variant	Exon 1 of 9		NP_001393844.1
HNF1A	XM_024449168.2	c.-160_-154delTGGGGGT		5_prime_UTR_variant	Exon 1 of 9		XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11	c.-160_-154delTGGGGGT		5_prime_UTR_variant	Exon 1 of 10	1	NM_000545.8	ENSP00000257555.5

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 145948 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000578 AC: 3 AN: 518880 Hom.: 0 AF XY: 0.00000718 AC XY: 2 AN XY: 278704

African (AFR) AF: 0.00 AC: 0 AN: 14974

American (AMR) AF: 0.00 AC: 0 AN: 31322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17514

East Asian (EAS) AF: 0.00 AC: 0 AN: 31280

South Asian (SAS) AF: 0.00 AC: 0 AN: 56524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2402

European-Non Finnish (NFE) AF: 0.00000985 AC: 3 AN: 304710

Other (OTH) AF: 0.00 AC: 0 AN: 28820

GnomAD4 genome AF: 0.0000137 AC: 2 AN: 145948 Hom.: 0 Cov.: 31 AF XY: 0.0000282 AC XY: 2 AN XY: 71004

African (AFR) AF: 0.0000256 AC: 1 AN: 39076

American (AMR) AF: 0.00 AC: 0 AN: 14824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 4810

South Asian (SAS) AF: 0.00 AC: 0 AN: 4524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66304

Other (OTH) AF: 0.00 AC: 0 AN: 1994

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

Splicing

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

Other links and lift over

dbSNP: rs538476099; hg19: chr12-121416400;