3-51389023-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_006010.6(MANF):​c.483C>T​(p.Ile161Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,612,148 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 6 hom., cov: 33)
Exomes 𝑓: 0.0033 ( 194 hom. )

Consequence

MANF
NM_006010.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.599
Variant links:
Genes affected
MANF (HGNC:15461): (mesencephalic astrocyte derived neurotrophic factor) The protein encoded by this gene is localized in the endoplasmic reticulum (ER) and golgi, and is also secreted. Reducing expression of this gene increases susceptibility to ER stress-induced death and results in cell proliferation. Activity of this protein is important in promoting the survival of dopaminergic neurons. The presence of polymorphisms in the N-terminal arginine-rich region, including a specific mutation that changes an ATG start codon to AGG, have been reported in a variety of solid tumors; however, these polymorphisms were later shown to exist in normal tissues and are thus no longer thought to be tumor-related. [provided by RefSeq, Apr 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 3-51389023-C-T is Benign according to our data. Variant chr3-51389023-C-T is described in ClinVar as [Benign]. Clinvar id is 733337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.599 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MANFNM_006010.6 linkc.483C>T p.Ile161Ile synonymous_variant Exon 4 of 4 ENST00000528157.7 NP_006001.5 P55145A8K878

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MANFENST00000528157.7 linkc.483C>T p.Ile161Ile synonymous_variant Exon 4 of 4 1 NM_006010.6 ENSP00000432799.3 P55145

Frequencies

GnomAD3 genomes
AF:
0.00182
AC:
277
AN:
152198
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0554
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00657
AC:
1615
AN:
245802
Hom.:
61
AF XY:
0.00908
AC XY:
1212
AN XY:
133446
show subpopulations
Gnomad AFR exome
AF:
0.000135
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0530
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000269
Gnomad OTH exome
AF:
0.00334
GnomAD4 exome
AF:
0.00326
AC:
4758
AN:
1459832
Hom.:
194
Cov.:
31
AF XY:
0.00478
AC XY:
3469
AN XY:
726010
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0525
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.00337
GnomAD4 genome
AF:
0.00183
AC:
278
AN:
152316
Hom.:
6
Cov.:
33
AF XY:
0.00286
AC XY:
213
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0557
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000470
Hom.:
0
Bravo
AF:
0.000366
Asia WGS
AF:
0.0200
AC:
69
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Apr 07, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
12
DANN
Benign
0.84
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.

Other links and lift over

dbSNP: rs371858457; hg19: chr3-51426454; API