chr22-43972324-A-G

Variant names:

• chr22-43972324-A-G
• rs3177036
• NM_015380.5:c.411A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015380.5(SAMM50):​c.411A>G​(p.Gly137Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,588,460 control chromosomes in the GnomAD database, including 230,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G137G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.58 (26765 hom., cov: 32)
  • Exomes 𝑓: 0.53 (203964 hom.)
• Consequence: SAMM50 NM_015380.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.553
• Publications: 20 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 22-43972324-A-G is Benign according to our data. Variant chr22-43972324-A-G is described in ClinVar as Benign. ClinVar VariationId is 1283359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.553 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

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.411A>G	p.Gly137Gly	synonymous	Exon 5 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.411A>G	p.Gly137Gly	synonymous	Exon 5 of 15	ENSP00000345445.4	Q9Y512
	SAMM50	ENST00000943220.1		c.411A>G	p.Gly137Gly	synonymous	Exon 5 of 15	ENSP00000613279.1
	SAMM50	ENST00000854677.1		c.411A>G	p.Gly137Gly	synonymous	Exon 5 of 15	ENSP00000524736.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88798 AN: 151924 Hom.: 26717 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.525

GnomAD2 exomes AF: 0.572 AC: 136052 AN: 237666 AF XY: 0.571

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.538

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.829

Gnomad FIN exome AF: 0.603

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.526 AC: 755054 AN: 1436420 Hom.: 203964 Cov.: 27 AF XY: 0.530 AC XY: 378519 AN XY: 714690

African (AFR) AF: 0.713 AC: 23169 AN: 32498

American (AMR) AF: 0.535 AC: 21337 AN: 39896

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 11459 AN: 25654

East Asian (EAS) AF: 0.850 AC: 33365 AN: 39248

South Asian (SAS) AF: 0.685 AC: 56154 AN: 81972

European-Finnish (FIN) AF: 0.610 AC: 32432 AN: 53174

Middle Eastern (MID) AF: 0.432 AC: 2447 AN: 5666

European-Non Finnish (NFE) AF: 0.494 AC: 542838 AN: 1098992

Other (OTH) AF: 0.537 AC: 31853 AN: 59320

GnomAD4 genome AF: 0.585 AC: 88897 AN: 152040 Hom.: 26765 Cov.: 32 AF XY: 0.590 AC XY: 43856 AN XY: 74340

African (AFR) AF: 0.711 AC: 29471 AN: 41456

American (AMR) AF: 0.530 AC: 8099 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3468

East Asian (EAS) AF: 0.827 AC: 4288 AN: 5182

South Asian (SAS) AF: 0.697 AC: 3366 AN: 4826

European-Finnish (FIN) AF: 0.608 AC: 6420 AN: 10560

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33922 AN: 67942

Other (OTH) AF: 0.531 AC: 1123 AN: 2114

Alfa AF: 0.527 Hom.: 75514

Bravo AF: 0.584

Asia WGS AF: 0.758 AC: 2637 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.1
DANN	Benign	0.79
PhyloP100		-0.55
Mutation Taster		=98/2	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: rs3177036; hg19: chr22-44368204; COSMIC: COSV63109448; COSMIC: COSV63109448;