rs2050156850

Variant names:

• chr22-43963301-C-G
• rs2050156850
• NM_015380.5:c.37C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-43963301-C-G
• chr22-43963301-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015380.5(SAMM50):​c.37C>G​(p.Pro13Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,457,338 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SAMM50 NM_015380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.52
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015380.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMM50	NM_015380.5	MANE Select	c.37C>G	p.Pro13Ala	missense	Exon 2 of 15	NP_056195.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMM50	ENST00000350028.5	TSL:1 MANE Select	c.37C>G	p.Pro13Ala	missense	Exon 2 of 15	ENSP00000345445.4	Q9Y512
	SAMM50	ENST00000943220.1		c.37C>G	p.Pro13Ala	missense	Exon 2 of 15	ENSP00000613279.1
	SAMM50	ENST00000854677.1		c.37C>G	p.Pro13Ala	missense	Exon 2 of 15	ENSP00000524736.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1457338 Hom.: 0 Cov.: 29 AF XY: 0.00000414 AC XY: 3 AN XY: 725240

African (AFR) AF: 0.00 AC: 0 AN: 33292

American (AMR) AF: 0.00 AC: 0 AN: 43556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39452

South Asian (SAS) AF: 0.00 AC: 0 AN: 85500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110186

Other (OTH) AF: 0.00 AC: 0 AN: 60158

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Benign	0.075	T
Sift4G	Benign	0.071	T
Polyphen		1.0	D
Vest4		0.54
MutPred		0.18		Gain of helix (P = 0.0164)
MVP		0.62
MPC		0.80
ClinPred		0.92	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.29
Mutation Taster		=243/57	polymorphism

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: rs2050156850; hg19: chr22-44359181;