7-101239854-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016068.3(FIS1):​c.411G>A​(p.Ala137Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0079 in 1,608,854 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 6 hom., cov: 33)
Exomes 𝑓: 0.0081 ( 70 hom. )

Consequence

FIS1
NM_016068.3 synonymous

Scores

1
11

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.81
Variant links:
Genes affected
FIS1 (HGNC:21689): (fission, mitochondrial 1) Enables identical protein binding activity. Involved in several processes, including calcium-mediated signaling using intracellular calcium source; cellular calcium ion homeostasis; and mitochondrion organization. Acts upstream of or within mitochondrion morphogenesis. Located in mitochondrion and peroxisome. Is integral component of mitochondrial outer membrane and integral component of peroxisomal membrane. Part of protein-containing complex. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008183837).
BP6
Variant 7-101239854-C-T is Benign according to our data. Variant chr7-101239854-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657857.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.81 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FIS1NM_016068.3 linkc.411G>A p.Ala137Ala synonymous_variant Exon 5 of 5 ENST00000223136.5 NP_057152.2 Q9Y3D6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FIS1ENST00000223136.5 linkc.411G>A p.Ala137Ala synonymous_variant Exon 5 of 5 1 NM_016068.3 ENSP00000223136.4 Q9Y3D6

Frequencies

GnomAD3 genomes
AF:
0.00579
AC:
881
AN:
152160
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00203
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.0154
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00860
Gnomad OTH
AF:
0.00384
GnomAD3 exomes
AF:
0.00592
AC:
1407
AN:
237616
Hom.:
6
AF XY:
0.00613
AC XY:
794
AN XY:
129510
show subpopulations
Gnomad AFR exome
AF:
0.00155
Gnomad AMR exome
AF:
0.00131
Gnomad ASJ exome
AF:
0.000613
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00177
Gnomad FIN exome
AF:
0.0104
Gnomad NFE exome
AF:
0.00976
Gnomad OTH exome
AF:
0.00467
GnomAD4 exome
AF:
0.00813
AC:
11836
AN:
1456576
Hom.:
70
Cov.:
31
AF XY:
0.00800
AC XY:
5790
AN XY:
724136
show subpopulations
Gnomad4 AFR exome
AF:
0.00153
Gnomad4 AMR exome
AF:
0.00145
Gnomad4 ASJ exome
AF:
0.000771
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00215
Gnomad4 FIN exome
AF:
0.0106
Gnomad4 NFE exome
AF:
0.00953
Gnomad4 OTH exome
AF:
0.00612
GnomAD4 genome
AF:
0.00579
AC:
881
AN:
152278
Hom.:
6
Cov.:
33
AF XY:
0.00608
AC XY:
453
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00202
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00249
Gnomad4 FIN
AF:
0.0154
Gnomad4 NFE
AF:
0.00860
Gnomad4 OTH
AF:
0.00380
Alfa
AF:
0.00661
Hom.:
2
Bravo
AF:
0.00464
TwinsUK
AF:
0.00593
AC:
22
ALSPAC
AF:
0.00727
AC:
28
ESP6500AA
AF:
0.00148
AC:
6
ESP6500EA
AF:
0.00733
AC:
61
ExAC
AF:
0.00558
AC:
674
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Mar 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

FIS1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
0.25
DANN
Benign
0.97
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.36
T
MetaRNN
Benign
0.0082
T
MetaSVM
Benign
-0.63
T
PROVEAN
Pathogenic
-8.0
D
REVEL
Benign
0.056
MutPred
0.17
Gain of methylation at G92 (P = 0.004);
MVP
0.54
ClinPred
0.076
T
GERP RS
-5.6
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6

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: rs183841255; hg19: chr7-100883135; COSMIC: COSV99778928; COSMIC: COSV99778928; API