rs2073082

Positions:

• chr22-43964127-G-A
• chr22-43964127-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.133-325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,962 control chromosomes in the GnomAD database, including 2,807 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 0.18 (2807 hom., cov: 31)
• Consequence: SAMM50 NM_015380.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733

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]

PNPLA3 (HGNC:18590): (patatin like phospholipase domain containing 3) The protein encoded by this gene is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMM50	NM_015380.5	c.133-325G>A		intron_variant		ENST00000350028.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMM50	ENST00000350028.5	c.133-325G>A		intron_variant		1	NM_015380.5	P1
PNPLA3	ENST00000406117.6	c.*961-325G>A		intron_variant, NMD_transcript_variant		2
SAMM50	ENST00000493161.1	n.315-325G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27257 AN: 151846 Hom.: 2799 Cov.: 31

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.180 AC: 27288 AN: 151962 Hom.: 2807 Cov.: 31 AF XY: 0.177 AC XY: 13171 AN XY: 74288

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.191

Alfa AF: 0.213 Hom.: 7403

Bravo AF: 0.175

Asia WGS AF: 0.287 AC: 998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.81

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: rs2073082; hg19: chr22-44360007;