22-43958231-C-T

Variant summary

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

The NM_015380.5(SAMM50):c.21+2633C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,060 control chromosomes in the GnomAD database, including 9,417 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 0.35 (9417 hom., cov: 33)
• Consequence: SAMM50 NM_015380.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMM50	NM_015380.5	c.21+2633C>T		intron_variant		ENST00000350028.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMM50	ENST00000350028.5	c.21+2633C>T		intron_variant		1	NM_015380.5	P1
PNPLA3	ENST00000406117.6	c.*850-5055C>T		intron_variant, NMD_transcript_variant		2
SAMM50	ENST00000493161.1	n.157+2633C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52644 AN: 151940 Hom.: 9412 Cov.: 33

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.346 AC: 52667 AN: 152060 Hom.: 9417 Cov.: 33 AF XY: 0.356 AC XY: 26421 AN XY: 74320

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.301

Alfa AF: 0.304 Hom.: 14444

Bravo AF: 0.341

Asia WGS AF: 0.446 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.3
Dann	Benign	0.62

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: rs738491; hg19: chr22-44354111;