Variant 22-43976189-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015380.5(SAMM50):c.777+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,597,940 control chromosomes in the GnomAD database, including 84,194 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13761 hom., cov: 32)

Exomes 𝑓: 0.30 ( 70433 hom. )

Consequence

SAMM50
NM_015380.5 splice_region, intron

Scores

Splicing: ADA: 0.00004198

Clinical Significance

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

Conservation

PhyloP100: 0.732

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]

SAMM50 links:

SAMM50 (HGNC:):

SAMM50 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-43976189-G-A is Benign according to our data. Variant chr22-43976189-G-A is described in ClinVar as [Benign]. Clinvar id is 1241496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMM50	NM_015380.5 linkuse as main transcript	c.777+6G>A		splice_region_variant, intron_variant		ENST00000350028.5	NP_056195.3	Q9Y512

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMM50	ENST00000350028.5 linkuse as main transcript	c.777+6G>A		splice_region_variant, intron_variant		1	NM_015380.5	ENSP00000345445.4		Q9Y512
SAMM50	ENST00000474323.5 linkuse as main transcript	n.1589+6G>A		splice_region_variant, intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60627

AN:

151904

Hom.:

13743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.360

AC:

90004

AN:

250240

Hom.:

17665

AF XY:

0.354

AC XY:

47927

AN XY:

135310

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.372

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.485

Gnomad SAS exome

AF:

0.431

Gnomad FIN exome

AF:

0.393

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.301

AC:

435519

AN:

1445918

Hom.:

70433

Cov.:

AF XY:

0.304

AC XY:

217779

AN XY:

715930

show subpopulations

Gnomad4 AFR exome

AF:

0.629

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.491

Gnomad4 SAS exome

AF:

0.425

Gnomad4 FIN exome

AF:

0.391

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.399

AC:

60683

AN:

152022

Hom.:

13761

Cov.:

AF XY:

0.406

AC XY:

30173

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.618

Gnomad4 AMR

AF:

0.358

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.436

Gnomad4 FIN

AF:

0.396

Gnomad4 NFE

AF:

0.275

Gnomad4 OTH

AF:

0.334

Alfa

AF:

0.339

Hom.:

4596

Bravo

AF:

0.406

Asia WGS

AF:

0.459

AC:

1598

AN:

3478

EpiCase

AF:

0.274

EpiControl

AF:

0.281

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 submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 05, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.7

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.026

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over