9-126614564-C-A

Variant names:

• chr9-126614564-C-A
• NM_001174147.2:c.115C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_001174147.2(LMX1B):​c.115C>A​(p.Pro39Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000346 in 1,443,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000035 (0 hom.)
• Consequence: LMX1B NM_001174147.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2035962).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1B	NM_001174147.2	c.115C>A	p.Pro39Thr	missense_variant	Exon 1 of 8	ENST00000373474.9	NP_001167618.1
LMX1B	NM_001174146.2	c.115C>A	p.Pro39Thr	missense_variant	Exon 1 of 8		NP_001167617.1
LMX1B	NM_002316.4	c.115C>A	p.Pro39Thr	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.115C>A	p.Pro39Thr	missense_variant	Exon 1 of 8	1	NM_001174147.2	ENSP00000362573.3
LMX1B	ENST00000355497.10	c.115C>A	p.Pro39Thr	missense_variant	Exon 1 of 8	1		ENSP00000347684.5
LMX1B	ENST00000526117.6	c.115C>A	p.Pro39Thr	missense_variant	Exon 1 of 8	1		ENSP00000436930.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1443446 Hom.: 0 Cov.: 31 AF XY: 0.00000418 AC XY: 3 AN XY: 717238

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: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000363

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.29	.;T;.;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	-0.41	N;N;N;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.23	N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.62	T;T;T;T
Sift4G	Benign	0.64	T;T;T;T
Polyphen		0.0	.;.;.;B
Vest4		0.45
MVP		0.41
MPC		0.81
ClinPred		0.69	D
GERP RS		3.0
Varity_R		0.067
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-129376843;