chr22-43972861-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015380.5(SAMM50):​c.430-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,539,410 control chromosomes in the GnomAD database, including 180,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26107 hom., cov: 31)
Exomes 𝑓: 0.49 ( 154253 hom. )

Consequence

SAMM50
NM_015380.5 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00001562
2

Clinical Significance

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

Conservation

PhyloP100: -0.596
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 22-43972861-C-T is Benign according to our data. Variant chr22-43972861-C-T is described in ClinVar as [Benign]. Clinvar id is 769164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAMM50NM_015380.5 linkuse as main transcriptc.430-10C>T splice_polypyrimidine_tract_variant, intron_variant ENST00000350028.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAMM50ENST00000350028.5 linkuse as main transcriptc.430-10C>T splice_polypyrimidine_tract_variant, intron_variant 1 NM_015380.5 P1
SAMM50ENST00000493161.1 linkuse as main transcriptn.612-10C>T splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.582
AC:
87338
AN:
150120
Hom.:
26062
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.709
Gnomad AMI
AF:
0.480
Gnomad AMR
AF:
0.528
Gnomad ASJ
AF:
0.464
Gnomad EAS
AF:
0.827
Gnomad SAS
AF:
0.697
Gnomad FIN
AF:
0.602
Gnomad MID
AF:
0.432
Gnomad NFE
AF:
0.496
Gnomad OTH
AF:
0.526
GnomAD3 exomes
AF:
0.506
AC:
103392
AN:
204356
Hom.:
22253
AF XY:
0.502
AC XY:
56059
AN XY:
111780
show subpopulations
Gnomad AFR exome
AF:
0.673
Gnomad AMR exome
AF:
0.480
Gnomad ASJ exome
AF:
0.408
Gnomad EAS exome
AF:
0.707
Gnomad SAS exome
AF:
0.601
Gnomad FIN exome
AF:
0.546
Gnomad NFE exome
AF:
0.440
Gnomad OTH exome
AF:
0.470
GnomAD4 exome
AF:
0.491
AC:
681980
AN:
1389184
Hom.:
154253
Cov.:
35
AF XY:
0.494
AC XY:
341534
AN XY:
691296
show subpopulations
Gnomad4 AFR exome
AF:
0.692
Gnomad4 AMR exome
AF:
0.504
Gnomad4 ASJ exome
AF:
0.423
Gnomad4 EAS exome
AF:
0.771
Gnomad4 SAS exome
AF:
0.632
Gnomad4 FIN exome
AF:
0.572
Gnomad4 NFE exome
AF:
0.463
Gnomad4 OTH exome
AF:
0.504
GnomAD4 genome
AF:
0.582
AC:
87432
AN:
150226
Hom.:
26107
Cov.:
31
AF XY:
0.587
AC XY:
43057
AN XY:
73298
show subpopulations
Gnomad4 AFR
AF:
0.710
Gnomad4 AMR
AF:
0.529
Gnomad4 ASJ
AF:
0.464
Gnomad4 EAS
AF:
0.827
Gnomad4 SAS
AF:
0.696
Gnomad4 FIN
AF:
0.602
Gnomad4 NFE
AF:
0.496
Gnomad4 OTH
AF:
0.531
Alfa
AF:
0.524
Hom.:
11085
Bravo
AF:
0.582

ClinVar

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

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.1
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000016
dbscSNV1_RF
Benign
0.0020
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: rs932430; hg19: chr22-44368741; API