chr1-165208094-TTGC-T

Variant names:

• chr1-165208094-TTGC-T
• rs144665555
• NM_177398.4:c.783_785delGCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_177398.4(LMX1A):​c.783_785delGCA​(p.Gln262del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000172 in 1,439,146 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LMX1A NM_177398.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67

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

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000172 (247/1439146) while in subpopulation SAS AF= 0.000285 (24/84104). AF 95% confidence interval is 0.000196. There are 0 homozygotes in gnomad4_exome. There are 107 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.783_785delGCA	p.Gln262del	disruptive_inframe_deletion	Exon 7 of 9	ENST00000342310.7	NP_796372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.783_785delGCA	p.Gln262del	disruptive_inframe_deletion	Exon 7 of 9	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.783_785delGCA	p.Gln262del	disruptive_inframe_deletion	Exon 6 of 8	1		ENSP00000356868.4
LMX1A	ENST00000489443.2	n.284_286delGCA		non_coding_transcript_exon_variant	Exon 4 of 7	1
LMX1A	ENST00000294816.6	c.783_785delGCA	p.Gln262del	disruptive_inframe_deletion	Exon 7 of 9	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 152104 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000172 AC: 247 AN: 1439146 Hom.: 0 AF XY: 0.000150 AC XY: 107 AN XY: 715216

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.000182

Gnomad4 ASJ exome AF: 0.000234

Gnomad4 EAS exome AF: 0.000154

Gnomad4 SAS exome AF: 0.000285

Gnomad4 FIN exome AF: 0.000591

Gnomad4 NFE exome AF: 0.000146

Gnomad4 OTH exome AF: 0.000118

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74312

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00564 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs144665555; hg19: chr1-165177331;