9-126614558-C-A

Variant names:

• chr9-126614558-C-A
• rs1012810702
• NM_001174147.2:c.109C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001174147.2(LMX1B):​c.109C>A​(p.Pro37Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,415,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LMX1B NM_001174147.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714

Genes affected

LMX1B (HGNC:6654): (LIM homeobox transcription factor 1 beta) This gene encodes a member of LIM-homeodomain family of proteins containing two N-terminal zinc-binding LIM domains, 1 homeodomain, and a C-terminal glutamine-rich domain. It functions as a transcription factor, and is essential for the normal development of dorsal limb structures, the glomerular basement membrane, the anterior segment of the eye, and dopaminergic and serotonergic neurons. Mutations in this gene are associated with nail-patella syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15334642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.109C>A	p.Pro37Thr	missense_variant	Exon 1 of 8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.109C>A	p.Pro37Thr	missense_variant	Exon 1 of 8		NP_001167617.1
LMX1B	NM_002316.4	c.109C>A	p.Pro37Thr	missense_variant	Exon 1 of 8		NP_002307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1B	ENST00000373474.9	c.109C>A	p.Pro37Thr	missense_variant	Exon 1 of 8	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.109C>A	p.Pro37Thr	missense_variant	Exon 1 of 8	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.109C>A	p.Pro37Thr	missense_variant	Exon 1 of 8	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1415844 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700312

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.32	.;T;.;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.85	D;D;D;D
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.0	N;N;N;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.060	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.46	T;T;T;T
Sift4G	Benign	0.74	T;T;T;T
Polyphen		0.0	.;.;.;B
Vest4		0.16
MVP		0.36
MPC		0.81
ClinPred		0.39	T
GERP RS		3.0
Varity_R		0.092
gMVP		0.49

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: rs1012810702; hg19: chr9-129376837;