rs587778398

chr12-120999579-AGCATCCAGC-GGCATCCAGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000545.8(HNF1A):c.1720_1729delinsGGCATCCAGG(p.Ser574_His577delinsGlyIleGlnAsp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNF1A NM_000545.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.45

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1A	NM_000545.8	c.1720_1729delinsGGCATCCAGG	p.Ser574_His577delinsGlyIleGlnAsp	missense_variant	9/10	ENST00000257555.11
HNF1A	NM_001306179.2	c.1741_1750delinsGGCATCCAGG	p.Ser581_His584delinsGlyIleGlnAsp	missense_variant	9/10
HNF1A	NM_001406915.1	c.1528_1537delinsGGCATCCAGG	p.Ser510_His513delinsGlyIleGlnAsp	missense_variant	8/9
HNF1A	XM_024449168.2	c.1813_1822delinsGGCATCCAGG	p.Ser605_His608delinsGlyIleGlnAsp	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A	ENST00000257555.11	c.1720_1729delinsGGCATCCAGG	p.Ser574_His577delinsGlyIleGlnAsp	missense_variant	9/10	1	NM_000545.8	P4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

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: rs587778398; hg19: chr12-121437382;