dbSNP rs753461629: LOXHD1:p.Glu972_Glu974del (chr18-46560222-CTCCTCTTCT-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_001384474.1(LOXHD1):c.2913_2921delAGAAGAGGA(p.Glu972_Glu974del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00014 in 1,551,910 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. E971E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

LOXHD1
NM_001384474.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 6.00

Variant links:

Genes affected

LOXHD1 (HGNC:26521): (lipoxygenase homology PLAT domains 1) This gene encodes a highly conserved protein consisting entirely of PLAT (polycystin/lipoxygenase/alpha-toxin) domains, thought to be involved in targeting proteins to the plasma membrane. Studies in mice show that this gene is expressed in the mechanosensory hair cells in the inner ear, and mutations in this gene lead to auditory defects, indicating that this gene is essential for normal hair cell function. Screening of human families segregating deafness identified a mutation in this gene which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2010]

LOXHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001384474.1

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXHD1	NM_001384474.1 link	c.2913_2921delAGAAGAGGA	p.Glu972_Glu974del	disruptive_inframe_deletion	Exon 19 of 41	ENST00000642948.1	NP_001371403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LOXHD1	ENST00000642948.1 link	c.2913_2921delAGAAGAGGA	p.Glu972_Glu974del	disruptive_inframe_deletion	Exon 19 of 41		NM_001384474.1	ENSP00000496347.1	A0A2R8Y7K4
LOXHD1	ENST00000536736.5 link	c.2913_2921delAGAAGAGGA	p.Glu972_Glu974del	disruptive_inframe_deletion	Exon 19 of 40	5		ENSP00000444586.1	F5GZB4
LOXHD1	ENST00000441551.6 link	c.2599-2742_2599-2734delAGAAGAGGA		intron_variant	Intron 18 of 38	5		ENSP00000387621.2	Q8IVV2-1
LOXHD1	ENST00000335730.6 link	n.2226_2234delAGAAGAGGA		non_coding_transcript_exon_variant	Exon 12 of 27	2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

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:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000296

AC:

AN:

158828

AF XY:

0.000419

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000653

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000146

AC:

204

AN:

1399594

Hom.:

AF XY:

0.000197

AC XY:

136

AN XY:

690296

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

31596

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

35702

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25182

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

35740

Gnomad4 SAS exome

AF:

0.00189

AC:

150

AN:

79232

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

49386

Gnomad4 NFE exome

AF:

0.0000343

AC:

AN:

1079010

Gnomad4 Remaining exome

AF:

0.000241

AC:

AN:

58046

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00249

AC:

0.00248756

AN:

0.00248756

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000294

AC:

0.0000293997

AN:

0.0000293997

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 77

Uncertain:2

Dec 13, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 06, 2019

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=148/52

polymorphism

Splicing

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