Variant 1-37794487-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001113482.2(MANEAL):c.305A>T(p.Tyr102Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000662 in 1,601,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

MANEAL
NM_001113482.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

MANEAL (HGNC:26452): (mannosidase endo-alpha like) Predicted to enable alpha-mannosidase activity. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

MANEAL 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=0.0753448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MANEAL	NM_001113482.2 linkuse as main transcript	c.305A>T	p.Tyr102Phe	missense_variant	1/4	ENST00000373045.11	NP_001106954.1
MANEAL	NM_001031740.3 linkuse as main transcript	c.305A>T	p.Tyr102Phe	missense_variant	1/4		NP_001026910.1
MANEAL	XM_005270510.4 linkuse as main transcript	c.305A>T	p.Tyr102Phe	missense_variant	1/3		XP_005270567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANEAL	ENST00000373045.11 linkuse as main transcript	c.305A>T	p.Tyr102Phe	missense_variant	1/4	1	NM_001113482.2	ENSP00000362136	P1	Q5VSG8-1
MANEAL	ENST00000397631.7 linkuse as main transcript	c.305A>T	p.Tyr102Phe	missense_variant	1/4	1		ENSP00000380755		Q5VSG8-3
MANEAL	ENST00000532512.1 linkuse as main transcript	c.5A>T	p.Tyr2Phe	missense_variant	1/3	4		ENSP00000432567

Frequencies

GnomAD3 genomes

AF:

0.0000792

AC:

AN:

151526

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000324

AC:

AN:

215958

Hom.:

AF XY:

0.0000417

AC XY:

AN XY:

119762

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000749

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000648

AC:

AN:

1450170

Hom.:

Cov.:

AF XY:

0.0000666

AC XY:

AN XY:

720546

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000840

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000792

AC:

AN:

151526

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73960

show subpopulations

Gnomad4 AFR

AF:

0.0000969

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000329

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000432

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

May 20, 2024

The c.305A>T (p.Y102F) alteration is located in exon 1 (coding exon 1) of the MANEAL gene. This alteration results from a A to T substitution at nucleotide position 305, causing the tyrosine (Y) at amino acid position 102 to be replaced by a phenylalanine (F). 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

0.089

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.028

T;.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.075

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

0.66

N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.51

N;N;N

REVEL

Benign

0.048

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.12

MVP

0.067

MPC

1.0

ClinPred

0.052

GERP RS

3.8

Varity_R

0.096

gMVP

0.51

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