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GeneBe

22-43973296-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_015380.5(SAMM50):c.621G>A(p.Thr207=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00486 in 1,605,488 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 185 hom., cov: 33)
Exomes 𝑓: 0.0026 ( 171 hom. )

Consequence

SAMM50
NM_015380.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.22
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 Benign. Variant got -15 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=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-43973296-G-A is Benign according to our data. Variant chr22-43973296-G-A is described in ClinVar as [Benign]. Clinvar id is 777732.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=-3.22 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAMM50NM_015380.5 linkuse as main transcriptc.621G>A p.Thr207= synonymous_variant 7/15 ENST00000350028.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAMM50ENST00000350028.5 linkuse as main transcriptc.621G>A p.Thr207= synonymous_variant 7/151 NM_015380.5 P1
SAMM50ENST00000493161.1 linkuse as main transcriptn.803G>A non_coding_transcript_exon_variant 7/73

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0265
AC:
4041
AN:
152204
Hom.:
185
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0918
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0109
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.0229
GnomAD3 exomes
AF:
0.00680
AC:
1710
AN:
251420
Hom.:
66
AF XY:
0.00498
AC XY:
677
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.0941
Gnomad AMR exome
AF:
0.00382
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000211
Gnomad OTH exome
AF:
0.00310
GnomAD4 exome
AF:
0.00259
AC:
3763
AN:
1453166
Hom.:
171
Cov.:
28
AF XY:
0.00224
AC XY:
1624
AN XY:
723548
show subpopulations
Gnomad4 AFR exome
AF:
0.0918
Gnomad4 AMR exome
AF:
0.00501
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000163
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000960
Gnomad4 OTH exome
AF:
0.00594
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0266
AC:
4047
AN:
152322
Hom.:
185
Cov.:
33
AF XY:
0.0258
AC XY:
1919
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0916
Gnomad4 AMR
AF:
0.0108
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.0227
Alfa
AF:
0.0111
Hom.:
40
Bravo
AF:
0.0305
Asia WGS
AF:
0.00549
AC:
19
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

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 testingInvitaeNov 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
0.54
Dann
Benign
0.50
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs34677401; hg19: chr22-44369176; API