Variant 17-36943007-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005568.5(LHX1):c.1097A>G(p.His366Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000102 in 1,609,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

LHX1
NM_005568.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.23

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05770713).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX1	NM_005568.5 linkuse as main transcript	c.1097A>G	p.His366Arg	missense_variant	5/5	ENST00000614239.1	NP_005559.2	P48742Q58F18
LHX1	XM_047435966.1 linkuse as main transcript	c.1097A>G	p.His366Arg	missense_variant	6/6		XP_047291922.1
LHX1	XM_047435967.1 linkuse as main transcript	c.1097A>G	p.His366Arg	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.1097A>G	p.His366Arg	missense_variant	5/5	1	NM_005568.5	ENSP00000477829.1	P48742
LHX1	ENST00000621767.1 linkuse as main transcript	c.68-235A>G		intron_variant		2		ENSP00000481496.1	A0A087WY40
ENSG00000276707	ENST00000614759.1 linkuse as main transcript	n.367+83T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

151200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000132

AC:

AN:

241834

Hom.:

AF XY:

0.000196

AC XY:

AN XY:

132744

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:

0.000921

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000109

AC:

159

AN:

1458434

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

725228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000929

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000331

AC:

AN:

151200

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73778

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000182

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Nov 22, 2022

The c.1097A>G (p.H366R) alteration is located in exon 5 (coding exon 5) of the LHX1 gene. This alteration results from a A to G substitution at nucleotide position 1097, causing the histidine (H) at amino acid position 366 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.31

Eigen

Benign

-0.11

Eigen_PC

Benign

0.061

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.024

MetaRNN

Benign

0.058

MetaSVM

Uncertain

-0.095

MutationAssessor

Benign

1.4

PrimateAI

Pathogenic

0.83

Sift4G

Benign

0.38

Polyphen

0.035

Vest4

0.29

MutPred

0.26

Gain of methylation at H366 (P = 0.1117);

MVP

0.37

ClinPred

0.082

GERP RS

4.7

Varity_R

0.47

gMVP

0.58

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