chr22-43972242-A-G

Position:

• chr22-43972242-A-G

Variant summary

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

The NM_015380.5(SAMM50):​c.329A>G​(p.Asp110Gly) variant causes a missense change. The variant allele was found at a frequency of 0.172 in 1,561,102 control chromosomes in the GnomAD database, including 25,689 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (2921 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22768 hom.)
• Consequence: SAMM50 NM_015380.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026952326).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMM50	NM_015380.5	c.329A>G	p.Asp110Gly	missense_variant	5/15	ENST00000350028.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMM50	ENST00000350028.5	c.329A>G	p.Asp110Gly	missense_variant	5/15	1	NM_015380.5	P1
SAMM50	ENST00000493161.1	n.511A>G		non_coding_transcript_exon_variant	5/7	3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28574 AN: 151974 Hom.: 2917 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.189

GnomAD3 exomes AF: 0.207 AC: 46333 AN: 223714 Hom.: 5623 AF XY: 0.202 AC XY: 24569 AN XY: 121430

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.386

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.171 AC: 240419 AN: 1409010 Hom.: 22768 Cov.: 27 AF XY: 0.172 AC XY: 120125 AN XY: 700424

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.188 AC: 28585 AN: 152092 Hom.: 2921 Cov.: 32 AF XY: 0.194 AC XY: 14407 AN XY: 74328

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.187

Alfa AF: 0.171 Hom.: 6107

Bravo AF: 0.192

TwinsUK AF: 0.157 AC: 584

ALSPAC AF: 0.167 AC: 642

ESP6500AA AF: 0.178 AC: 786

ESP6500EA AF: 0.156 AC: 1339

ExAC AF: 0.207 AC: 25125

Asia WGS AF: 0.270 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.045
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	6.5e-9	P;P
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.080
Sift	Benign	0.21	T
Sift4G	Benign	0.11	T
Polyphen		0.010	B
Vest4		0.080
MPC		0.36
ClinPred		0.019	T
GERP RS		4.8
Varity_R		0.23
gMVP		0.54

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: rs3761472; hg19: chr22-44368122; COSMIC: COSV63109505; COSMIC: COSV63109505;