22-43998522-C-T

Position:

• chr22-43998522-C-T

Variant summary

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

The ENST00000465768.1(SAMM50):​n.79+8116C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,104 control chromosomes in the GnomAD database, including 3,328 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 0.20 (3328 hom., cov: 32)
• Consequence: SAMM50 ENST00000465768.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436

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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMM50	ENST00000465768.1	n.79+8116C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30898 AN: 151986 Hom.: 3326 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.203 AC: 30902 AN: 152104 Hom.: 3328 Cov.: 32 AF XY: 0.209 AC XY: 15535 AN XY: 74336

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.221

Alfa AF: 0.180 Hom.: 3202

Bravo AF: 0.210

Asia WGS AF: 0.272 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2073080; hg19: chr22-44394402;