NM_022363.3:c.1150G>A

Variant names:

• chr12-113463249-C-T
• NM_022363.3:c.1150G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022363.3(LHX5):​c.1150G>A​(p.Gly384Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LHX5 NM_022363.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50
• Publications: 0 publications found

Genes affected

LHX5 (HGNC:14216): (LIM homeobox 5) This gene encodes a protein belonging to a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein may function as a transcriptional regulator and be involved in the control of differentiation and development of the forebrain. In mice, this protein is essential for the regulation of precursor cell proliferation and the control of neuronal differentiation and migration during hippocampal development. This protein is involved in learning and motor functions in adult mice. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.289896).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022363.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX5	NM_022363.3	MANE Select	c.1150G>A	p.Gly384Ser	missense	Exon 5 of 5	NP_071758.1	Q9H2C1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX5	ENST00000261731.4	TSL:1 MANE Select	c.1150G>A	p.Gly384Ser	missense	Exon 5 of 5	ENSP00000261731.2	Q9H2C1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1374362 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 678464

African (AFR) AF: 0.00 AC: 0 AN: 28644

American (AMR) AF: 0.00 AC: 0 AN: 34366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24436

East Asian (EAS) AF: 0.00 AC: 0 AN: 33434

South Asian (SAS) AF: 0.00 AC: 0 AN: 78524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073538

Other (OTH) AF: 0.00 AC: 0 AN: 57166

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.013
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.60	N
PhyloP100		4.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.18
Sift	Benign	0.27	T
Sift4G	Benign	0.79	T
Polyphen		0.011	B
Vest4		0.13
MutPred		0.34		Gain of catalytic residue at Y385 (P = 0)
MVP		0.73
ClinPred		0.77	D
GERP RS		4.1
Varity_R		0.20
gMVP		0.22
Mutation Taster		=82/18	polymorphism

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

hg19: chr12-113901054;