Genetic Variant HMGA1:c.*82A>T (chr6-34244966-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145899.3(HMGA1):c.*82A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HMGA1
NM_145899.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Publications

12 publications found

Variant links:

Genes affected

HMGA1 (HGNC:5010): (high mobility group AT-hook 1) This gene encodes a chromatin-associated protein involved in the regulation of gene transcription, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells. The encoded protein preferentially binds to the minor groove of AT-rich regions in double-stranded DNA. Multiple transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene have been identified on multiple chromosomes. [provided by RefSeq, Jan 2016]

HMGA1 Gene-Disease associations (from GenCC):

type 2 diabetes mellitus
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

HMGA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145899.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGA1	NM_145899.3	MANE Select	c.*82A>T	3_prime_UTR	Exon 6 of 6	NP_665906.1	P17096-1
HMGA1	NM_001319078.2		c.*82A>T	3_prime_UTR	Exon 5 of 5	NP_001306007.1	P17096-1
HMGA1	NM_001319079.2		c.*82A>T	3_prime_UTR	Exon 6 of 6	NP_001306008.1	P17096-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGA1	ENST00000311487.9	TSL:1 MANE Select	c.*82A>T	3_prime_UTR	Exon 6 of 6	ENSP00000308227.4	P17096-1
HMGA1	ENST00000447654.5	TSL:1	c.*82A>T	3_prime_UTR	Exon 5 of 5	ENSP00000399888.1	P17096-1
HMGA1	ENST00000347617.10	TSL:1	c.*82A>T	3_prime_UTR	Exon 5 of 5	ENSP00000288245.9	P17096-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

146064

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1351672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

667810

African (AFR)

AF:

0.00

AC:

AN:

30572

American (AMR)

AF:

0.00

AC:

AN:

34884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24598

East Asian (EAS)

AF:

0.00

AC:

AN:

35072

South Asian (SAS)

AF:

0.00

AC:

AN:

78108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4180

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1040768

Other (OTH)

AF:

0.00

AC:

AN:

55966

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

146064

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70950

African (AFR)

AF:

0.00

AC:

AN:

39042

American (AMR)

AF:

0.00

AC:

AN:

14674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

4808

South Asian (SAS)

AF:

0.00

AC:

AN:

4588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66592

Other (OTH)

AF:

0.00

AC:

AN:

2002

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.11

(source)

DANN

Benign

0.93

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over