Variant rs16855642 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033343.4(LHX4):c.450C>G(p.Asn150Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N150N) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LHX4
NM_033343.4 missense, splice_region

Scores

Splicing: ADA: 0.0003636

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.769

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LHX4	NM_033343.4 linkuse as main transcript	c.450C>G	p.Asn150Lys	missense_variant, splice_region_variant	3/6	ENST00000263726.4
LHX4	XM_011510105.3 linkuse as main transcript	c.267C>G	p.Asn89Lys	missense_variant, splice_region_variant	3/6
LHX4	XM_011510106.4 linkuse as main transcript	c.267C>G	p.Asn89Lys	missense_variant, splice_region_variant	3/6
LHX4	XM_011510108.3 linkuse as main transcript	c.225C>G	p.Asn75Lys	missense_variant, splice_region_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHX4	ENST00000263726.4 linkuse as main transcript	c.450C>G	p.Asn150Lys	missense_variant, splice_region_variant	3/6	1	NM_033343.4	P1
LHX4	ENST00000561113.1 linkuse as main transcript	c.389C>G	p.Thr130Arg	missense_variant, splice_region_variant, NMD_transcript_variant	2/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250414

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135440

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727108

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.074

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.47

MutationAssessor

Benign

-0.65

MutationTaster

Benign

0.000016

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

1.7

REVEL

Uncertain

0.40

Sift

Benign

0.77

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.56

MutPred

0.38

Gain of ubiquitination at N150 (P = 7e-04);

MVP

0.81

MPC

0.33

ClinPred

0.031

GERP RS

-2.1

Varity_R

0.14

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00036

dbscSNV1_RF

Benign

0.034

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over