Variant 1-180271836-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM1PP3BP4_StrongBP6_Moderate

The NM_033343.4(LHX4):c.608T>G(p.Val203Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00060 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LHX4
NM_033343.4 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

LHX4 (HGNC:21734): (LIM homeobox 4) 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 involved in the control of differentiation and development of the pituitary gland. Mutations in this gene cause combined pituitary hormone deficiency 4. [provided by RefSeq, Dec 2010]

LHX4 links:

ACBD6 (HGNC:23339): (acyl-CoA binding domain containing 6) Predicted to enable fatty-acyl-CoA binding activity and lipid binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACBD6 links:

ACBD6 (HGNC:):

ACBD6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM1

In a DNA_binding_region Homeobox (size 59) in uniprot entity LHX4_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_033343.4

PP3

Multiple lines of computational evidence support a deleterious effect 10: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.020503074).

BP6

Variant 1-180271836-T-G is Benign according to our data. Variant chr1-180271836-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 801582.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX4	NM_033343.4 linkuse as main transcript	c.608T>G	p.Val203Gly	missense_variant, splice_region_variant	5/6	ENST00000263726.4	NP_203129.1	Q969G2A0A0S2Z5S4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX4	ENST00000263726.4 linkuse as main transcript	c.608T>G	p.Val203Gly	missense_variant, splice_region_variant	5/6	1	NM_033343.4	ENSP00000263726.2		Q969G2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151410

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000603

AC:

881

AN:

1460868

Hom.:

Cov.:

AF XY:

0.000594

AC XY:

432

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000963

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00149

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0106

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

151410

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73884

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000634

Hom.:

ExAC

AF:

0.0261

AC:

3170

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Short stature-pituitary and cerebellar defects-small sella turcica syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.96

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

MetaRNN

Benign

0.021

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.4

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-6.4

REVEL

Pathogenic

0.99

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.23

MPC

1.1

ClinPred

0.039

GERP RS

5.6

Varity_R

0.99

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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