Genetic Variant NM_177398.4:c.670-76A>G (chr1-165210852-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_177398.4(LMX1A):c.670-76A>G variant causes a intron 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000046 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LMX1A
NM_177398.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.922

Publications

16 publications found

Variant links:

Genes affected

LMX1A (HGNC:6653): (LIM homeobox transcription factor 1 alpha) This gene encodes a homeodomain and LIM-domain containing protein. The encoded protein is a transcription factor that acts as a positive regulator of insulin gene transcription. This gene also plays a role in the development of dopamine producing neurons during embryogenesis. Mutations in this gene are associated with an increased risk of developing Parkinson's disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

LMX1A links:

LMX1A-AS2 (HGNC:40343): (LMX1A antisense RNA 2)

LMX1A-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4 link	c.670-76A>G		intron_variant	Intron 5 of 8	ENST00000342310.7	NP_796372.1	Q8TE12-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7 link	c.670-76A>G		intron_variant	Intron 5 of 8	2	NM_177398.4	ENSP00000340226.3		Q8TE12-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000460

AC:

AN:

868732

Hom.:

Cov.:

AF XY:

0.00000449

AC XY:

AN XY:

445694

show subpopulations

African (AFR)

AF:

0.0000954

AC:

AN:

20966

American (AMR)

AF:

0.00

AC:

AN:

33654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20022

East Asian (EAS)

AF:

0.0000292

AC:

AN:

34294

South Asian (SAS)

AF:

0.00

AC:

AN:

59690

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4454

European-Non Finnish (NFE)

AF:

0.00000165

AC:

AN:

607156

Other (OTH)

AF:

0.00

AC:

AN:

39924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

20034

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.16

(source)

DANN

Benign

0.61

PhyloP100

-0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: -1

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

Publications

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NM_177398.4:c.670-76A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over