Variant 9-5906952-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005511.2(MLANA):c.242A>T(p.His81Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,600,914 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

MLANA
NM_005511.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0580

Variant links:

Genes affected

MLANA (HGNC:7124): (melan-A) Located in endoplasmic reticulum membrane; melanosome; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

MLANA links:

BRD10 (HGNC:23378): (bromodomain containing 10)

BRD10 links:

MLANA (HGNC:):

MLANA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014631003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLANA	NM_005511.2 linkuse as main transcript	c.242A>T	p.His81Leu	missense_variant	4/5	ENST00000381477.8	NP_005502.1	Q16655A0A384MR46

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLANA	ENST00000381477.8 linkuse as main transcript	c.242A>T	p.His81Leu	missense_variant	4/5	1	NM_005511.2	ENSP00000370886.3		Q16655

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000300

AC:

AN:

236652

Hom.:

AF XY:

0.000350

AC XY:

AN XY:

128536

show subpopulations

Gnomad AFR exome

AF:

0.000200

Gnomad AMR exome

AF:

0.0000321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000305

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000464

AC:

672

AN:

1448532

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

326

AN XY:

720612

show subpopulations

Gnomad4 AFR exome

AF:

0.000185

Gnomad4 AMR exome

AF:

0.0000237

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00113

Gnomad4 FIN exome

AF:

0.0000751

Gnomad4 NFE exome

AF:

0.000491

Gnomad4 OTH exome

AF:

0.000368

GnomAD4 genome

AF:

0.000217

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74526

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000335

Hom.:

Bravo

AF:

0.000204

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000395

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 20, 2024

The c.242A>T (p.H81L) alteration is located in exon 4 (coding exon 3) of the MLANA gene. This alteration results from a A to T substitution at nucleotide position 242, causing the histidine (H) at amino acid position 81 to be replaced by a leucine (L). 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

0.084

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.41

CADD

Benign

4.5

DANN

Benign

0.90

DEOGEN2

Benign

0.20

T;T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.28

.;.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.094

Sift

Benign

0.81

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.32

MVP

0.22

MPC

0.29

ClinPred

0.020

GERP RS

-0.64

Varity_R

0.075

gMVP

0.28

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