Variant chr1-37794204-G-A 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.22G>A(p.Ala8Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000177 in 1,299,630 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 0.000087 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

MANEAL
NM_001113482.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

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=0.108323485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MANEAL	NM_001113482.2 link	c.22G>A	p.Ala8Thr	missense_variant	1/4	ENST00000373045.11	NP_001106954.1	Q5VSG8-1
MANEAL	NM_001031740.3 link	c.22G>A	p.Ala8Thr	missense_variant	1/4		NP_001026910.1	Q5VSG8-3
MANEAL	XM_005270510.4 link	c.22G>A	p.Ala8Thr	missense_variant	1/3		XP_005270567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANEAL	ENST00000373045.11 link	c.22G>A	p.Ala8Thr	missense_variant	1/4	1	NM_001113482.2	ENSP00000362136.6		Q5VSG8-1
MANEAL	ENST00000397631.7 link	c.22G>A	p.Ala8Thr	missense_variant	1/4	1		ENSP00000380755.3		Q5VSG8-3

Frequencies

GnomAD3 genomes

AF:

0.0000872

AC:

AN:

149004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000865

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000869

AC:

AN:

1150626

Hom.:

Cov.:

AF XY:

0.0000106

AC XY:

AN XY:

566412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000171

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000106

Gnomad4 OTH exome

AF:

0.0000932

GnomAD4 genome

AF:

0.0000872

AC:

AN:

149004

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

72586

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000865

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000298

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

Oct 06, 2021

The c.22G>A (p.A8T) alteration is located in exon 1 (coding exon 1) of the MANEAL gene. This alteration results from a G to A substitution at nucleotide position 22, causing the alanine (A) at amino acid position 8 to be replaced by a threonine (T). 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

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.70

T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.96

D;D

Vest4

0.20

MutPred

0.35

Gain of phosphorylation at A8 (P = 0.0524);Gain of phosphorylation at A8 (P = 0.0524);

MVP

0.15

MPC

1.1

ClinPred

0.23

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.098

gMVP

0.64

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