Variant 1-165203979-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_177398.4(LMX1A):c.1050T>C(p.Asp350=) variant causes a synonymous change. The variant allele was found at a frequency of 1 in 1,614,162 control chromosomes in the GnomAD database, including 806,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75984 hom., cov: 31)

Exomes 𝑓: 1.0 ( 730784 hom. )

Consequence

LMX1A
NM_177398.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.70

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-165203979-A-G is Benign according to our data. Variant chr1-165203979-A-G is described in ClinVar as [Benign]. Clinvar id is 1294826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LMX1A	NM_177398.4 linkuse as main transcript	c.1050T>C	p.Asp350=	synonymous_variant	9/9	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2 linkuse as main transcript	c.1050T>C	p.Asp350=	synonymous_variant	9/9		NP_001167540.1
LMX1A	XM_011509538.4 linkuse as main transcript	c.810T>C	p.Asp270=	synonymous_variant	7/7		XP_011507840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7 linkuse as main transcript	c.1050T>C	p.Asp350=	synonymous_variant	9/9	2	NM_177398.4	ENSP00000340226	P1	Q8TE12-1
LMX1A	ENST00000367893.4 linkuse as main transcript	c.1050T>C	p.Asp350=	synonymous_variant	8/8	1		ENSP00000356868	P1	Q8TE12-1
LMX1A	ENST00000489443.2 linkuse as main transcript	n.684T>C		non_coding_transcript_exon_variant	7/7	1
LMX1A	ENST00000294816.6 linkuse as main transcript	c.1050T>C	p.Asp350=	synonymous_variant	9/9	2		ENSP00000294816	P1	Q8TE12-1

Frequencies

GnomAD3 genomes

AF:

0.999

AC:

152010

AN:

152170

Hom.:

75925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.996

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.999

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD3 exomes

AF:

1.00

AC:

251399

AN:

251476

Hom.:

125661

AF XY:

1.00

AC XY:

135877

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.996

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1461720

AN:

1461874

Hom.:

730784

Cov.:

AF XY:

1.00

AC XY:

727177

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.996

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.999

AC:

152128

AN:

152288

Hom.:

75984

Cov.:

AF XY:

0.999

AC XY:

74365

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.996

Gnomad4 AMR

AF:

0.999

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

0.999

Hom.:

22086

Bravo

AF:

0.999

Asia WGS

AF:

0.999

AC:

3476

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Autosomal dominant nonsyndromic hearing loss 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over