Variant 1-37799670-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001113482.2(MANEAL):c.841G>T(p.Ala281Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,890 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: 0.0000055 ( 0 hom. )

Consequence

MANEAL
NM_001113482.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2759151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MANEAL	NM_001113482.2 linkuse as main transcript	c.841G>T	p.Ala281Ser	missense_variant	4/4	ENST00000373045.11	NP_001106954.1
MANEAL	NM_152496.3 linkuse as main transcript	c.175G>T	p.Ala59Ser	missense_variant	2/2		NP_689709.1
MANEAL	NM_001031740.3 linkuse as main transcript	c.738-174G>T		intron_variant			NP_001026910.1
MANEAL	XM_005270510.4 linkuse as main transcript	c.661-174G>T		intron_variant			XP_005270567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANEAL	ENST00000373045.11 linkuse as main transcript	c.841G>T	p.Ala281Ser	missense_variant	4/4	1	NM_001113482.2	ENSP00000362136	P1	Q5VSG8-1
	ENST00000433474.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727246

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

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

Mar 29, 2023

The c.841G>T (p.A281S) alteration is located in exon 4 (coding exon 4) of the MANEAL gene. This alteration results from a G to T substitution at nucleotide position 841, causing the alanine (A) at amino acid position 281 to be replaced by a serine (S). 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

0.075

BayesDel_addAF

Benign

0.0032

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

T;.;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.054

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Uncertain

0.37

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.79

N;N;N

REVEL

Uncertain

0.45

Sift

Benign

0.088

T;T;T

Sift4G

Benign

0.094

T;T;T

Polyphen

0.41

B;.;B

Vest4

0.11

MutPred

0.51

Gain of disorder (P = 0.0377);.;.;

MVP

0.82

MPC

0.18

ClinPred

0.79

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.44

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over