Variant 17-36942812-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The ENST00000614239.1(LHX1):c.902C>A(p.Pro301Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000598 in 1,556,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

LHX1
ENST00000614239.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.773

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LHX1	NM_005568.5 linkuse as main transcript	c.902C>A	p.Pro301Gln	missense_variant	5/5	ENST00000614239.1	NP_005559.2
LHX1	XM_047435966.1 linkuse as main transcript	c.902C>A	p.Pro301Gln	missense_variant	6/6		XP_047291922.1
LHX1	XM_047435967.1 linkuse as main transcript	c.902C>A	p.Pro301Gln	missense_variant	6/6		XP_047291923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LHX1	ENST00000614239.1 linkuse as main transcript	c.902C>A	p.Pro301Gln	missense_variant	5/5	1	NM_005568.5	ENSP00000477829	P1
	ENST00000614759.1 linkuse as main transcript	n.367+278G>T		intron_variant, non_coding_transcript_variant		5
LHX1	ENST00000621767.1 linkuse as main transcript	c.69-430C>A		intron_variant		2		ENSP00000481496

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152260

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000248

AC:

AN:

201718

Hom.:

AF XY:

0.00000906

AC XY:

AN XY:

110366

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:

0.0000548

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000620

AC:

AN:

1403754

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

690908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000769

Gnomad4 OTH exome

AF:

0.0000694

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74390

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000581

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000414

AC:

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

Mar 06, 2023

The c.902C>A (p.P301Q) alteration is located in exon 5 (coding exon 5) of the LHX1 gene. This alteration results from a C to A substitution at nucleotide position 902, causing the proline (P) at amino acid position 301 to be replaced by a glutamine (Q). 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

0.32

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.98

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.77

MetaSVM

Pathogenic

0.81

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.60

MVP

0.41

ClinPred

0.76

GERP RS

4.1

Varity_R

0.42

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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