chr22-43972979-C-T

Variant names:

• chr22-43972979-C-T
• rs771203161
• NM_015380.5:c.538C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015380.5(SAMM50):​c.538C>T​(p.Arg180Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000113 in 1,592,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: SAMM50 NM_015380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11462006).

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.538C>T	p.Arg180Trp	missense	Exon 6 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.538C>T	p.Arg180Trp	missense	Exon 6 of 15	ENSP00000345445.4	Q9Y512
	SAMM50	ENST00000943220.1		c.538C>T	p.Arg180Trp	missense	Exon 6 of 15	ENSP00000613279.1
	SAMM50	ENST00000854677.1		c.538C>T	p.Arg180Trp	missense	Exon 6 of 15	ENSP00000524736.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000161 AC: 37 AN: 230522 AF XY: 0.000160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000215

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.000249

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000112 AC: 162 AN: 1440524 Hom.: 0 Cov.: 33 AF XY: 0.000105 AC XY: 75 AN XY: 716198

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.000188 AC: 7 AN: 37284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25482

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.000148 AC: 12 AN: 80828

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53298

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5688

European-Non Finnish (NFE) AF: 0.000119 AC: 132 AN: 1107154

Other (OTH) AF: 0.000118 AC: 7 AN: 59574

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.000109

EpiControl AF: 0.000297

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	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.0066
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.8
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.079
Sift	Benign	0.030	D
Sift4G	Uncertain	0.026	D
Polyphen		0.0	B
Vest4		0.34
MVP		0.59
MPC		0.29
ClinPred		0.093	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.46
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs771203161; hg19: chr22-44368859; COSMIC: COSV63109460;