Variant 9-136197599-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS1

The NM_178138.6(LHX3):c.920G>A(p.Arg307Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,548,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R307P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

LHX3
NM_178138.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81

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 Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01775533).

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000329 (46/1396084) while in subpopulation EAS AF= 0.000607 (22/36218). AF 95% confidence interval is 0.000411. There are 0 homozygotes in gnomad4_exome. There are 23 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX3	NM_178138.6 link	c.920G>A	p.Arg307Gln	missense_variant	6/6	ENST00000371748.10	NP_835258.1	Q9UBR4-1F1T0D5
LHX3	NM_014564.5 link	c.935G>A	p.Arg312Gln	missense_variant	6/6		NP_055379.1	Q9UBR4-2F1T0D9
LHX3	NM_001363746.1 link	c.887G>A	p.Arg296Gln	missense_variant	6/6		NP_001350675.1
LHX3	XM_017015168.1 link	c.848G>A	p.Arg283Gln	missense_variant	6/6		XP_016870657.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LHX3	ENST00000371748.10 link	c.920G>A	p.Arg307Gln	missense_variant	6/6	1	NM_178138.6	ENSP00000360813.4	Q9UBR4-1
LHX3	ENST00000371746.9 link	c.935G>A	p.Arg312Gln	missense_variant	6/6	1		ENSP00000360811.3	Q9UBR4-2
LHX3	ENST00000619587.1 link	c.887G>A	p.Arg296Gln	missense_variant	6/6	1		ENSP00000483080.1	F1T0D7
LHX3	ENST00000645419.1 link	n.1745G>A		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000263

AC:

AN:

151868

Hom.:

AF XY:

0.0000121

AC XY:

AN XY:

82636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad SAS exome

AF:

0.0000857

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1396084

Hom.:

Cov.:

AF XY:

0.0000334

AC XY:

AN XY:

687896

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000607

Gnomad4 SAS exome

AF:

0.0000250

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000176

Gnomad4 OTH exome

AF:

0.0000519

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000174

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.20

.;T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.60

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-0.28

.;N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

0.18

N;N;.

REVEL

Benign

0.15

Sift

Benign

0.83

T;T;.

Sift4G

Benign

0.70

T;T;T

Polyphen

0.0030

.;B;.

Vest4

0.045

MutPred

0.19

.;Gain of loop (P = 0.2754);.;

MVP

0.75

MPC

0.012

ClinPred

0.0087

GERP RS

0.99

Varity_R

0.028

gMVP

0.36

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over