1-197929128-C-A

Position:

• chr1-197929128-C-A

Variant summary

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

The NM_020204.3(LHX9):​c.1063C>A​(p.Pro355Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LHX9 NM_020204.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.54

Genes affected

LHX9 (HGNC:14222): (LIM homeobox 9) This gene encodes a member of the LIM homeobox gene family of developmentally expressed transcription factors. The encoded protein contains a homeodomain and two cysteine-rich zinc-binding LIM domains involved in protein-protein interactions. The protein is highly similar to a mouse protein that causes gonadal agenesis when inactivated, suggesting a role in gonadal development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX9	NM_020204.3	c.1063C>A	p.Pro355Thr	missense_variant	5/5	ENST00000367387.6	NP_064589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX9	ENST00000367387.6	c.1063C>A	p.Pro355Thr	missense_variant	5/5	1	NM_020204.3	ENSP00000356357.4
LHX9	ENST00000367390.7	c.1036C>A	p.Pro346Thr	missense_variant	6/6	1		ENSP00000356360.3
LHX9	ENST00000561173.5	c.954+1335C>A		intron_variant		5		ENSP00000453064.1
LHX9	ENST00000367391.5	c.909+1335C>A		intron_variant		5		ENSP00000356361.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pituitary stalk interruption syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Human Developmental Genetics, Institut Pasteur

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Benign	0.97	.;L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.56
Sift	Uncertain	0.012	D;D
Sift4G	Benign	0.084	T;T
Polyphen		1.0	D;D
Vest4		0.48
MutPred		0.27		.;Gain of glycosylation at P355 (P = 0.0201);
MVP		0.81
MPC		1.6
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.19
gMVP		0.54

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: chr1-197898258;