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1-117466336-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_006699.5(MAN1A2):c.1077T>G(p.Val359=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,595,296 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 19 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 15 hom. )

Consequence

MAN1A2
NM_006699.5 splice_region, synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40
Variant links:
Genes affected
MAN1A2 (HGNC:6822): (mannosidase alpha class 1A member 2) Alpha-mannosidases function at different stages of N-glycan maturation in mammalian cells. See MAN2A1 (MIM 154582) for general information.[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-117466336-T-G is Benign according to our data. Variant chr1-117466336-T-G is described in ClinVar as [Benign]. Clinvar id is 708356.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.4 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00735 (1119/152266) while in subpopulation AFR AF= 0.0245 (1018/41570). AF 95% confidence interval is 0.0232. There are 19 homozygotes in gnomad4. There are 554 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 16 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAN1A2NM_006699.5 linkuse as main transcriptc.1077T>G p.Val359= splice_region_variant, synonymous_variant 8/13 ENST00000356554.7
MAN1A2XM_006710302.4 linkuse as main transcriptc.1077T>G p.Val359= splice_region_variant, synonymous_variant 8/14
MAN1A2XM_011540536.4 linkuse as main transcriptc.1077T>G p.Val359= splice_region_variant, synonymous_variant 8/13
MAN1A2XM_017000115.2 linkuse as main transcriptc.950+24011T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAN1A2ENST00000356554.7 linkuse as main transcriptc.1077T>G p.Val359= splice_region_variant, synonymous_variant 8/131 NM_006699.5 P1
MAN1A2ENST00000449370.6 linkuse as main transcriptc.276T>G p.Val92= splice_region_variant, synonymous_variant 4/92

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00718
AC:
1093
AN:
152148
Hom.:
16
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0239
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
Gnomad ASJ
AF:
0.0101
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00250
AC:
616
AN:
246806
Hom.:
6
AF XY:
0.00203
AC XY:
271
AN XY:
133566
show subpopulations
Gnomad AFR exome
AF:
0.0250
Gnomad AMR exome
AF:
0.00154
Gnomad ASJ exome
AF:
0.0127
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000669
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000277
Gnomad OTH exome
AF:
0.00101
GnomAD4 exome
AF:
0.00104
AC:
1507
AN:
1443030
Hom.:
15
Cov.:
26
AF XY:
0.000970
AC XY:
697
AN XY:
718922
show subpopulations
Gnomad4 AFR exome
AF:
0.0243
Gnomad4 AMR exome
AF:
0.00166
Gnomad4 ASJ exome
AF:
0.0122
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000105
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000127
Gnomad4 OTH exome
AF:
0.00278
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00735
AC:
1119
AN:
152266
Hom.:
19
Cov.:
32
AF XY:
0.00744
AC XY:
554
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0245
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.0101
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00804
Alfa
AF:
0.00329
Hom.:
1
Bravo
AF:
0.00836
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 02, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
8.6
Dann
Benign
0.80

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.

Other links and lift over

dbSNP: rs34355735; hg19: chr1-118008958; API