Variant chr1-197929226-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000367387.6(LHX9):c.1161C>T(p.Ser387=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,535,984 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 165 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 141 hom. )

Consequence

LHX9
ENST00000367387.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.43

Variant links:

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]

LHX9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 1-197929226-C-T is Benign according to our data. Variant chr1-197929226-C-T is described in ClinVar as [Benign]. Clinvar id is 777332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX9	NM_020204.3 linkuse as main transcript	c.1161C>T	p.Ser387=	synonymous_variant	5/5	ENST00000367387.6	NP_064589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX9	ENST00000367387.6 linkuse as main transcript	c.1161C>T	p.Ser387=	synonymous_variant	5/5	1	NM_020204.3	ENSP00000356357	P1	Q9NQ69-1
LHX9	ENST00000367390.7 linkuse as main transcript	c.1134C>T	p.Ser378=	synonymous_variant	6/6	1		ENSP00000356360		Q9NQ69-2
LHX9	ENST00000367391.5 linkuse as main transcript	c.909+1433C>T		intron_variant		5		ENSP00000356361		Q9NQ69-3
LHX9	ENST00000561173.5 linkuse as main transcript	c.954+1433C>T		intron_variant		5		ENSP00000453064

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3898

AN:

151830

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000288

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00678

AC:

1482

AN:

218562

Hom.:

AF XY:

0.00481

AC XY:

576

AN XY:

119748

show subpopulations

Gnomad AFR exome

AF:

0.0907

Gnomad AMR exome

AF:

0.00415

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000517

Gnomad FIN exome

AF:

0.0000944

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00541

GnomAD4 exome

AF:

0.00309

AC:

4275

AN:

1384038

Hom.:

141

Cov.:

AF XY:

0.00279

AC XY:

1916

AN XY:

687666

show subpopulations

Gnomad4 AFR exome

AF:

0.0895

Gnomad4 AMR exome

AF:

0.00482

Gnomad4 ASJ exome

AF:

0.0000416

Gnomad4 EAS exome

AF:

0.0000279

Gnomad4 SAS exome

AF:

0.000628

Gnomad4 FIN exome

AF:

0.000100

Gnomad4 NFE exome

AF:

0.000765

Gnomad4 OTH exome

AF:

0.00634

GnomAD4 genome

AF:

0.0257

AC:

3902

AN:

151946

Hom.:

165

Cov.:

AF XY:

0.0244

AC XY:

1810

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0867

Gnomad4 AMR

AF:

0.0123

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000288

Gnomad4 NFE

AF:

0.00109

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0297

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.70

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