Variant chr1-37794687-G-C 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.505G>C(p.Glu169Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,454,526 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: not found (cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

MANEAL
NM_001113482.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

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:

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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=0.1081382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MANEAL	NM_001113482.2 link	c.505G>C	p.Glu169Gln	missense_variant	1/4	ENST00000373045.11	NP_001106954.1	Q5VSG8-1
MANEAL	NM_001031740.3 link	c.505G>C	p.Glu169Gln	missense_variant	1/4		NP_001026910.1	Q5VSG8-3
MANEAL	XM_005270510.4 link	c.505G>C	p.Glu169Gln	missense_variant	1/3		XP_005270567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MANEAL	ENST00000373045.11 link	c.505G>C	p.Glu169Gln	missense_variant	1/4	1	NM_001113482.2	ENSP00000362136.6	Q5VSG8-1
MANEAL	ENST00000397631.7 link	c.505G>C	p.Glu169Gln	missense_variant	1/4	1		ENSP00000380755.3	Q5VSG8-3
MANEAL	ENST00000532512.1 link	c.205G>C	p.Glu69Gln	missense_variant	1/3	4		ENSP00000432567.1	H0YCZ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1454526

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

723348

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:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000332

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

Jul 19, 2022

The c.505G>C (p.E169Q) alteration is located in exon 1 (coding exon 1) of the MANEAL gene. This alteration results from a G to C substitution at nucleotide position 505, causing the glutamic acid (E) at amino acid position 169 to be replaced by a glutamine (Q). 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

0.090

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

T;.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.052

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.0093

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;L;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.22

N;N;N

REVEL

Benign

0.019

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.17

B;B;.

Vest4

0.063

MutPred

0.14

Loss of glycosylation at S165 (P = 0.1634);Loss of glycosylation at S165 (P = 0.1634);.;

MVP

0.20

MPC

1.5

ClinPred

0.33

GERP RS

3.7

Varity_R

0.11

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

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

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