22-43958231-C-T

Variant names:

• chr22-43958231-C-T
• rs738491
• NM_015380.5:c.21+2633C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SAMM50	NM_015380.5	c.21+2633C>T		intron_variant	Intron 1 of 14	ENST00000350028.5	NP_056195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMM50	ENST00000350028.5	c.21+2633C>T		intron_variant	Intron 1 of 14	1	NM_015380.5	ENSP00000345445.4
PNPLA3	ENST00000406117.6	n.*850-5055C>T		intron_variant	Intron 8 of 9	2		ENSP00000384668.2
SAMM50	ENST00000493161.1	n.157+2633C>T		intron_variant	Intron 1 of 6	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

African (AFR) AF: 0.390 AC: 16164 AN: 41466

American (AMR) AF: 0.350 AC: 5353 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1018 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2520 AN: 5156

South Asian (SAS) AF: 0.451 AC: 2178 AN: 4830

European-Finnish (FIN) AF: 0.432 AC: 4555 AN: 10556

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19789 AN: 67988

Other (OTH) AF: 0.301 AC: 634 AN: 2104

Alfa AF: 0.312 Hom.: 23686

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
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs738491; hg19: chr22-44354111;