chr1-165344190-A-G

Variant names:

• chr1-165344190-A-G
• rs1395548
• NM_177398.4:c.263+8886T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177398.4(LMX1A):​c.263+8886T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.263+8886T>C		intron_variant	Intron 3 of 8	ENST00000342310.7	NP_796372.1
LMX1A	NM_001174069.2	c.263+8886T>C		intron_variant	Intron 3 of 8		NP_001167540.1
LMX1A	XM_011509540.3	c.263+8886T>C		intron_variant	Intron 3 of 7		XP_011507842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.263+8886T>C		intron_variant	Intron 3 of 8	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.263+8886T>C		intron_variant	Intron 2 of 7	1		ENSP00000356868.4
LMX1A	ENST00000294816.6	c.263+8886T>C		intron_variant	Intron 3 of 8	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.74
PhyloP100		0.22

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: rs1395548; hg19: chr1-165313427;