22-43976189-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015380.5(SAMM50):c.777+6G>A variant causes a splice donor 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. 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_donor_region, intron
• Scores: Splicing: ADA: 0.00004198
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.732

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
SAMM50	NM_015380.5	c.777+6G>A		splice_donor_region_variant, intron_variant		ENST00000350028.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMM50	ENST00000350028.5	c.777+6G>A		splice_donor_region_variant, intron_variant		1	NM_015380.5	P1
SAMM50	ENST00000474323.5	n.1589+6G>A		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60627 AN: 151904 Hom.: 13743 Cov.: 32

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

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.: 32 AF XY: 0.304 AC XY: 217779 AN XY: 715930

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.: 32 AF XY: 0.406 AC XY: 30173 AN XY: 74280

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs2073084; hg19: chr22-44372069; COSMIC: COSV63109509; COSMIC: COSV63109509;