Variant 17-36942878-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005568.5(LHX1):c.968C>T(p.Pro323Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,442,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

LHX1
NM_005568.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.89

Variant links:

Genes affected

LHX1 (HGNC:6593): (LIM homeobox 1) This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor important for the development of the renal and urogenital systems. This gene is a candidate for Mayer-Rokitansky-Kuster-Hauser syndrome, a disorder characterized by anomalies in the female genital tract. [provided by RefSeq, Dec 2010]

LHX1 links:

ENSG00000276707 (HGNC:):

ENSG00000276707 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX1	NM_005568.5 linkuse as main transcript	c.968C>T	p.Pro323Leu	missense_variant	5/5	ENST00000614239.1	NP_005559.2	P48742Q58F18
LHX1	XM_047435966.1 linkuse as main transcript	c.968C>T	p.Pro323Leu	missense_variant	6/6		XP_047291922.1
LHX1	XM_047435967.1 linkuse as main transcript	c.968C>T	p.Pro323Leu	missense_variant	6/6		XP_047291923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LHX1	ENST00000614239.1 linkuse as main transcript	c.968C>T	p.Pro323Leu	missense_variant	5/5	1	NM_005568.5	ENSP00000477829.1	P48742
LHX1	ENST00000621767.1 linkuse as main transcript	c.68-364C>T		intron_variant		2		ENSP00000481496.1	A0A087WY40
ENSG00000276707	ENST00000614759.1 linkuse as main transcript	n.367+212G>A		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000481

AC:

AN:

207804

Hom.:

AF XY:

0.00

AC XY:

AN XY:

113948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1442038

Hom.:

Cov.:

AF XY:

0.00000559

AC XY:

AN XY:

715580

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.968C>T (p.P323L) alteration is located in exon 5 (coding exon 5) of the LHX1 gene. This alteration results from a C to T substitution at nucleotide position 968, causing the proline (P) at amino acid position 323 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

0.66

MutationAssessor

Benign

1.8

PrimateAI

Pathogenic

0.79

Sift4G

Benign

0.093

Polyphen

0.99

Vest4

0.42

MutPred

0.28

Loss of loop (P = 0.0603);

MVP

0.72

ClinPred

0.95

GERP RS

4.5

Varity_R

0.52

gMVP

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over