rs2143571

Positions:

• chr22-43995806-G-A
• chr22-43995806-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015380.5(SAMM50):​c.1365-532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,152 control chromosomes in the GnomAD database, including 5,334 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5334 hom., cov: 33)
• Consequence: SAMM50 NM_015380.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SAMM50	NM_015380.5	c.1365-532G>A		intron_variant		ENST00000350028.5	NP_056195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMM50	ENST00000350028.5	c.1365-532G>A		intron_variant		1	NM_015380.5	ENSP00000345445.4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38305 AN: 152034 Hom.: 5328 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38327 AN: 152152 Hom.: 5334 Cov.: 33 AF XY: 0.256 AC XY: 19024 AN XY: 74380

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.253

Alfa AF: 0.194 Hom.: 6311

Bravo AF: 0.266

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.15

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

Other links and lift over

dbSNP: rs2143571; hg19: chr22-44391686;