2-159743083-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001282805.2(MARCHF7):​c.176C>T​(p.Ala59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,613,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

MARCHF7
NM_001282805.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.57
Variant links:
Genes affected
MARCHF7 (HGNC:17393): (membrane associated ring-CH-type finger 7) MARCH7 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). MARCH proteins add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their vesicular transport between membrane compartments (Bartee et al., 2004 [PubMed 14722266]).[supplied by OMIM, Mar 2010]

Genome browser will be placed here

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=0.077492476).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MARCHF7NM_001282805.2 linkc.176C>T p.Ala59Val missense_variant Exon 5 of 12 ENST00000409175.6 NP_001269734.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MARCHF7ENST00000409175.6 linkc.176C>T p.Ala59Val missense_variant Exon 5 of 12 2 NM_001282805.2 ENSP00000386830.1 Q9H992-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000156
AC:
39
AN:
250600
Hom.:
0
AF XY:
0.000170
AC XY:
23
AN XY:
135452
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000582
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000462
Gnomad NFE exome
AF:
0.000212
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000198
AC:
290
AN:
1461288
Hom.:
0
Cov.:
30
AF XY:
0.000197
AC XY:
143
AN XY:
726920
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000656
Gnomad4 NFE exome
AF:
0.000212
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000239
Hom.:
0
Bravo
AF:
0.000174
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000140
AC:
17
EpiCase
AF:
0.000218
EpiControl
AF:
0.000356

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 20, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.176C>T (p.A59V) alteration is located in exon 3 (coding exon 2) of the MARCH7 gene. This alteration results from a C to T substitution at nucleotide position 176, causing the alanine (A) at amino acid position 59 to be replaced by a valine (V). 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
0.091
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
23
DANN
Benign
0.96
DEOGEN2
Benign
0.0097
T;T;T;T;.
Eigen
Benign
0.11
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.89
D;.;D;D;D
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.077
T;T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.69
.;N;N;.;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.44
N;N;N;N;N
REVEL
Benign
0.060
Sift
Benign
0.10
T;T;T;T;D
Sift4G
Benign
0.080
T;T;T;T;T
Polyphen
0.52
P;P;P;.;.
Vest4
0.27
MVP
0.29
MPC
0.071
ClinPred
0.045
T
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.14
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs149235126; hg19: chr2-160599594; COSMIC: COSV99373689; COSMIC: COSV99373689; API