chr12-120999311-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000545.8(HNF1A):​c.1545G>C​(p.Thr515=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T515T) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

HNF1A
NM_000545.8 synonymous

Scores

9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20120981).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HNF1ANM_000545.8 linkuse as main transcriptc.1545G>C p.Thr515= synonymous_variant 8/10 ENST00000257555.11 NP_000536.6
HNF1ANM_001306179.2 linkuse as main transcriptc.1545G>C p.Thr515= synonymous_variant 8/10 NP_001293108.2
HNF1ANM_001406915.1 linkuse as main transcriptc.1353G>C p.Thr451= synonymous_variant 7/9 NP_001393844.1
HNF1AXM_024449168.2 linkuse as main transcriptc.1545G>C p.Thr515= synonymous_variant 8/9 XP_024304936.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HNF1AENST00000257555.11 linkuse as main transcriptc.1545G>C p.Thr515= synonymous_variant 8/101 NM_000545.8 ENSP00000257555 P4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
49
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
6.2
DANN
Benign
0.76
DEOGEN2
Benign
0.26
T
FATHMM_MKL
Benign
0.073
N
LIST_S2
Benign
0.47
T
MetaRNN
Benign
0.20
T
MutationTaster
Benign
1.0
D;D;D;D
Sift4G
Benign
0.12
T
Vest4
0.29
MVP
0.79
GERP RS
-7.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

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: chr12-121437114; COSMIC: COSV56567209; COSMIC: COSV56567209; API