Variant 1-37795832-C-G 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.646C>G(p.Gln216Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MANEAL
NM_001113482.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

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=0.16445202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MANEAL	NM_001113482.2 linkuse as main transcript	c.646C>G	p.Gln216Glu	missense_variant	2/4	ENST00000373045.11	NP_001106954.1
MANEAL	NM_001031740.3 linkuse as main transcript	c.646C>G	p.Gln216Glu	missense_variant	2/4		NP_001026910.1
MANEAL	NM_152496.3 linkuse as main transcript	c.57C>G	p.Ile19Met	missense_variant	1/2		NP_689709.1
MANEAL	XM_005270510.4 linkuse as main transcript	c.646C>G	p.Gln216Glu	missense_variant	2/3		XP_005270567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MANEAL	ENST00000373045.11 linkuse as main transcript	c.646C>G	p.Gln216Glu	missense_variant	2/4	1	NM_001113482.2	ENSP00000362136	P1	Q5VSG8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248952

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134812

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461768

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jun 22, 2023

The c.646C>G (p.Q216E) alteration is located in exon 2 (coding exon 2) of the MANEAL gene. This alteration results from a C to G substitution at nucleotide position 646, causing the glutamine (Q) at amino acid position 216 to be replaced by a glutamic acid (E). 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

0.068

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.46

M_CAP

Benign

0.028

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.34

MutationTaster

Benign

0.98

D;D;D;N

PROVEAN

Benign

0.12

REVEL

Benign

0.051

Sift

Benign

0.036

Sift4G

Uncertain

0.029

Polyphen

0.29

Vest4

0.20

MutPred

0.30

Gain of disorder (P = 0.0278);

MVP

0.40

ClinPred

0.86

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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