rs1553512

Variant names:

• chr1-165202576-T-A
• rs1553512
• NM_177398.4:c.*1304A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 7

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• Mobius syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.*1304A>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.*1304A>T		3_prime_UTR_variant	Exon 9 of 9		NP_001167540.1
LMX1A	XM_011509538.4	c.*1304A>T		3_prime_UTR_variant	Exon 7 of 7		XP_011507840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.*1304A>T		3_prime_UTR_variant	Exon 9 of 9	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000294816.6	c.*1304A>T		3_prime_UTR_variant	Exon 9 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.286 AC: 11844 AN: 41450

American (AMR) AF: 0.0551 AC: 843 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0351 AC: 122 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.00498 AC: 24 AN: 4818

European-Finnish (FIN) AF: 0.0141 AC: 149 AN: 10596

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0155 AC: 1051 AN: 67998

Other (OTH) AF: 0.0839 AC: 177 AN: 2110

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
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1553512; hg19: chr1-165171813;