chr15-59207382-C-T

Position:

chr15-59207382-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting

The ENST00000288235.9(MYO1E):c.1530+1299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,870 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

MYO1E
ENST00000288235.9 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Variant links:

Genes affected

LDHAL6B (HGNC:21481): (lactate dehydrogenase A like 6B) Predicted to enable L-lactate dehydrogenase activity. Predicted to be involved in pyruvate metabolic process. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LDHAL6B links:

MYO1E (HGNC:7599): (myosin IE) This gene encodes a member of the nonmuscle class I myosins which are a subgroup of the unconventional myosin protein family. The unconventional myosin proteins function as actin-based molecular motors. Class I myosins are characterized by a head (motor) domain, a regulatory domain and a either a short or long tail domain. Among the class I myosins, this protein is distinguished by a long tail domain that is involved in crosslinking actin filaments. This protein localizes to the cytoplasm and may be involved in intracellular movement and membrane trafficking. Mutations in this gene are the cause of focal segmental glomerulosclerosis-6. This gene has been referred to as myosin IC in the literature but is distinct from the myosin IC gene located on chromosome 17. [provided by RefSeq, Jan 2012]

MYO1E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32971922).

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000239 (35/1461716) while in subpopulation AFR AF= 0.0000597 (2/33476). AF 95% confidence interval is 0.0000183. There are 0 homozygotes in gnomad4_exome. There are 17 alleles in male gnomad4_exome subpopulation. Median coverage is 37. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDHAL6B	NM_033195.3 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	1/1	ENST00000307144.6	NP_149972.1
MYO1E	NM_004998.4 linkuse as main transcript	c.1530+1299G>A		intron_variant		ENST00000288235.9	NP_004989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDHAL6B	ENST00000307144.6 linkuse as main transcript	c.442C>T	p.Arg148Cys	missense_variant	1/1		NM_033195.3	ENSP00000302393	P1
MYO1E	ENST00000288235.9 linkuse as main transcript	c.1530+1299G>A		intron_variant		1	NM_004998.4	ENSP00000288235	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251196

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461716

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Jun 17, 2024

The c.442C>T (p.R148C) alteration is located in exon 1 (coding exon 1) of the LDHAL6B gene. This alteration results from a C to T substitution at nucleotide position 442, causing the arginine (R) at amino acid position 148 to be replaced by a cysteine (C). 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0079

MetaRNN

Benign

0.33

MetaSVM

Uncertain

0.0028

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.35

Sift

Uncertain

0.021

Sift4G

Benign

0.13

Polyphen

0.59

Vest4

0.36

MVP

0.82

MPC

0.023

ClinPred

0.86

GERP RS

0.47

Varity_R

0.37

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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