22-43976109-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015380.5(SAMM50):ā€‹c.703C>Gā€‹(p.Leu235Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,612,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

SAMM50
NM_015380.5 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51
Variant links:
Genes affected
SAMM50 (HGNC:24276): (SAMM50 sorting and assembly machinery component) This gene encodes a component of the Sorting and Assembly Machinery (SAM) of the mitochondrial outer membrane. The Sam complex functions in the assembly of beta-barrel proteins into the outer mitochondrial membrane.[provided by RefSeq, Jun 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SAMM50NM_015380.5 linkuse as main transcriptc.703C>G p.Leu235Val missense_variant 8/15 ENST00000350028.5 NP_056195.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SAMM50ENST00000350028.5 linkuse as main transcriptc.703C>G p.Leu235Val missense_variant 8/151 NM_015380.5 ENSP00000345445 P1
SAMM50ENST00000474323.5 linkuse as main transcriptn.1515C>G non_coding_transcript_exon_variant 1/82

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251448
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
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:
0.00000479
AC:
7
AN:
1460490
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000177
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
AF:
0.0000131
AC:
2
AN:
152212
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsMay 02, 2024The c.703C>G (p.L235V) alteration is located in exon 8 (coding exon 8) of the SAMM50 gene. This alteration results from a C to G substitution at nucleotide position 703, causing the leucine (L) at amino acid position 235 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
0.15
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.039
T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.63
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.99
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.12
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.023
D
Polyphen
0.94
P
Vest4
0.78
MutPred
0.66
Loss of helix (P = 0.1299);
MVP
0.37
MPC
0.70
ClinPred
0.46
T
GERP RS
5.3
Varity_R
0.33
gMVP
0.37

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: rs752221535; hg19: chr22-44371989; API