Variant 9-122228662-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000394319.9(LHX6):c.79G>T(p.Asp27Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,146,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

LHX6
ENST00000394319.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.716

Variant links:

Genes affected

LHX6 (HGNC:21735): (LIM homeobox 6) This gene encodes a member of a large protein family that contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein has tandem LIM domains as well as a DNA-binding homeodomain. The protein functions as a transcription factor involved in embryogenesis and head development and is highly expressed in neural crest derived mesenchyme cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]

LHX6 links:

LHX6 (HGNC:):

LHX6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.42157423).

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LHX6	NM_014368.5 linkuse as main transcript	c.79G>T	p.Asp27Tyr	missense_variant	1/10	ENST00000394319.9	NP_055183.2
LHX6	NM_199160.4 linkuse as main transcript	c.79G>T	p.Asp27Tyr	missense_variant	1/9		NP_954629.2
LHX6	XM_005251916.4 linkuse as main transcript	c.79G>T	p.Asp27Tyr	missense_variant	1/6		XP_005251973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LHX6	ENST00000394319.9 linkuse as main transcript	c.79G>T	p.Asp27Tyr	missense_variant	1/10	1	NM_014368.5	ENSP00000377854.4	Q9UPM6-3
LHX6	ENST00000340587.7 linkuse as main transcript	c.79G>T	p.Asp27Tyr	missense_variant	1/9	1		ENSP00000340137.3	Q9UPM6-4
LHX6	ENST00000559529.1 linkuse as main transcript	n.420G>T		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000148

AC:

AN:

1146180

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

550378

show subpopulations

Gnomad4 AFR exome

AF:

0.0000434

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000656

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000146

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

The c.79G>T (p.D27Y) alteration is located in exon 1 (coding exon 1) of the LHX6 gene. This alteration results from a G to T substitution at nucleotide position 79, causing the aspartic acid (D) at amino acid position 27 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.0047

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.98

Eigen

Benign

0.12

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.42

T;T

MetaSVM

Uncertain

0.024

MutationTaster

Benign

0.53

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.72

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

0.90

P;P

Vest4

0.23

MutPred

0.34

Gain of phosphorylation at D27 (P = 0.0233);Gain of phosphorylation at D27 (P = 0.0233);

MVP

0.61

MPC

2.2

ClinPred

0.94

GERP RS

3.2

gMVP

0.29

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