chr1-165205901-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_177398.4(LMX1A):c.951C>T(p.Thr317Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,614,056 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 31 hom. )

Consequence

LMX1A
NM_177398.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.672

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 1-165205901-G-A is Benign according to our data. Variant chr1-165205901-G-A is described in ClinVar as [Benign]. Clinvar id is 777953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.672 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0106 (1616/152236) while in subpopulation AFR AF = 0.037 (1538/41530). AF 95% confidence interval is 0.0355. There are 17 homozygotes in GnomAd4. There are 740 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4 link	c.951C>T	p.Thr317Thr	synonymous_variant	Exon 8 of 9	ENST00000342310.7	NP_796372.1	Q8TE12-1
LMX1A	NM_001174069.2 link	c.951C>T	p.Thr317Thr	synonymous_variant	Exon 8 of 9		NP_001167540.1	Q8TE12-1
LMX1A	XM_011509538.4 link	c.711C>T	p.Thr237Thr	synonymous_variant	Exon 6 of 7		XP_011507840.1
LMX1A-AS2	XR_922234.2 link	n.366+131G>A		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LMX1A	ENST00000342310.7 link	c.951C>T	p.Thr317Thr	synonymous_variant	Exon 8 of 9	2	NM_177398.4	ENSP00000340226.3	Q8TE12-1
LMX1A	ENST00000367893.4 link	c.951C>T	p.Thr317Thr	synonymous_variant	Exon 7 of 8	1		ENSP00000356868.4	Q8TE12-1
LMX1A	ENST00000489443.2 link	n.585C>T		non_coding_transcript_exon_variant	Exon 6 of 7	1
LMX1A	ENST00000294816.6 link	c.951C>T	p.Thr317Thr	synonymous_variant	Exon 8 of 9	2		ENSP00000294816.2	Q8TE12-1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1614

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0371

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00275

AC:

692

AN:

251398

AF XY:

0.00185

show subpopulations

Gnomad AFR exome

AF:

0.0375

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00120

AC:

1751

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

728

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.0390

AC:

1304

AN:

33468

American (AMR)

AF:

0.00195

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000185

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00314

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.000123

AC:

137

AN:

1112006

Other (OTH)

AF:

0.00313

AC:

189

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

168

251

335

419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0106

AC:

1616

AN:

152236

Hom.:

Cov.:

AF XY:

0.00994

AC XY:

740

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0370

AC:

1538

AN:

41530

American (AMR)

AF:

0.00372

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68016

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

152

229

305

381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00377

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

LMX1A-related disorder

Benign:1

May 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.5

(source)

DANN

Benign

0.76

PhyloP100

0.67

Mutation Taster

=97/3

polymorphism

(source)

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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chr1-165205901-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over