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. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

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. Variant has been reported in Lovd as Benign (no stars).

• 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 12-120978597-AGGGTTGG-A is Benign according to our data. Variant chr12-120978597-AGGGTTGG-A is described in Lovd as [Benign].

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	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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000985

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0000256

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs538476099; hg19: chr12-121416400;