Variant chr9-136196500-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_178138.6(LHX3):c.*825C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00824 in 152,380 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 29 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LHX3
NM_178138.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.579

Variant links:

Genes affected

LHX3 (HGNC:6595): (LIM homeobox 3) This gene encodes a member of a large family of proteins which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor that is required for pituitary development and motor neuron specification. Mutations in this gene cause combined pituitary hormone deficiency 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

LHX3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-136196500-G-T is Benign according to our data. Variant chr9-136196500-G-T is described in ClinVar as [Benign]. Clinvar id is 365799.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
LHX3	NM_178138.6 linkuse as main transcript	c.*825C>A	3_prime_UTR_variant	6/6	ENST00000371748.10
LHX3	NM_001363746.1 linkuse as main transcript	c.*825C>A	3_prime_UTR_variant	6/6
LHX3	NM_014564.5 linkuse as main transcript	c.*825C>A	3_prime_UTR_variant	6/6
LHX3	XM_017015168.1 linkuse as main transcript	c.*825C>A	3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHX3	ENST00000371748.10 linkuse as main transcript	c.*825C>A	3_prime_UTR_variant	6/6	1	NM_178138.6		Q9UBR4-1
LHX3	ENST00000371746.9 linkuse as main transcript	c.*825C>A	3_prime_UTR_variant	6/6	1		P1	Q9UBR4-2
LHX3	ENST00000619587.1 linkuse as main transcript	c.*825C>A	3_prime_UTR_variant	6/6	1
LHX3	ENST00000645419.1 linkuse as main transcript	n.2844C>A	non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes

AF:

0.00820

AC:

1249

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0321

Gnomad SAS

AF:

0.0899

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00669

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

436

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

254

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00824

AC:

1256

AN:

152380

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

754

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0322

Gnomad4 SAS

AF:

0.0894

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00476

Hom.:

Bravo

AF:

0.00753

Asia WGS

AF:

0.0700

AC:

241

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Non-acquired combined pituitary hormone deficiency with spine abnormalities

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.4

DANN

Benign

0.84

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