chr12-120996556-GGCCCCCTC-CCCCCT

Variant names:

• chr12-120996556-GGCCCCCTC-CCCCCT
• NM_000545.8:c.1123_1131delGGCCCCCTCinsCCCCCT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP3

The NM_000545.8(HNF1A):​c.1123_1131delGGCCCCCTCinsCCCCCT​(p.Gly375_Leu377delinsProPro) variant causes a missense, conservative inframe deletion change involving the alteration of a conserved nucleotide. 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, conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.99

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000545.8. Strenght limited to Supporting due to length of the change: 1aa.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1A	NM_000545.8	c.1123_1131delGGCCCCCTCinsCCCCCT	p.Gly375_Leu377delinsProPro	missense_variant, conservative_inframe_deletion		ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2	c.1123_1131delGGCCCCCTCinsCCCCCT	p.Gly375_Leu377delinsProPro	missense_variant, conservative_inframe_deletion			NP_001293108.2
HNF1A	NM_001406915.1	c.1123_1131delGGCCCCCTCinsCCCCCT	p.Gly375_Leu377delinsProPro	missense_variant, conservative_inframe_deletion			NP_001393844.1
HNF1A	XM_024449168.2	c.1123_1131delGGCCCCCTCinsCCCCCT	p.Gly375_Leu377delinsProPro	missense_variant, conservative_inframe_deletion			XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11	c.1123_1131delGGCCCCCTCinsCCCCCT	p.Gly375_Leu377delinsProPro	missense_variant, conservative_inframe_deletion		1	NM_000545.8	ENSP00000257555.5

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-121434359;