rs6006473

Variant names:

• chr22-43997195-C-T
• rs6006473
• ENST00000465768.1:n.79+6789C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000465768.1(SAMM50):​n.79+6789C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,054 control chromosomes in the GnomAD database, including 17,409 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 0.47 (17409 hom., cov: 33)
• Consequence: SAMM50 ENST00000465768.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMM50	ENST00000465768.1	n.79+6789C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71358 AN: 151936 Hom.: 17402 Cov.: 33

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.469 AC: 71388 AN: 152054 Hom.: 17409 Cov.: 33 AF XY: 0.473 AC XY: 35184 AN XY: 74330

African (AFR) AF: 0.602 AC: 24969 AN: 41474

American (AMR) AF: 0.464 AC: 7098 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2521 AN: 5152

South Asian (SAS) AF: 0.475 AC: 2287 AN: 4818

European-Finnish (FIN) AF: 0.472 AC: 4983 AN: 10550

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.393 AC: 26690 AN: 67984

Other (OTH) AF: 0.450 AC: 949 AN: 2110

Alfa AF: 0.440 Hom.: 9695

Bravo AF: 0.475

Asia WGS AF: 0.483 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.74
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6006473; hg19: chr22-44393075;