rs1553512

Positions:

• chr1-165202576-T-A
• chr1-165202576-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177398.4(LMX1A):​c.*1304A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 152,112 control chromosomes in the GnomAD database, including 1,791 homozygotes. 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 0.094 (1791 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: LMX1A NM_177398.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.*1304A>T		3_prime_UTR_variant	9/9	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.*1304A>T		3_prime_UTR_variant	9/9		NP_001167540.1
LMX1A	XM_011509538.4	c.*1304A>T		3_prime_UTR_variant	7/7		XP_011507840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.*1304A>T		3_prime_UTR_variant	9/9	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000294816.6	c.*1304A>T		3_prime_UTR_variant	9/9	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14249 AN: 151994 Hom.: 1786 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00581

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0848

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0938 AC: 14268 AN: 152112 Hom.: 1791 Cov.: 31 AF XY: 0.0906 AC XY: 6741 AN XY: 74370

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.0551

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.0155

Gnomad4 OTH AF: 0.0839

Alfa AF: 0.00327 Hom.: 1

Bravo AF: 0.108

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs1553512; hg19: chr1-165171813;