22-43982119-C-T

Position:

• chr22-43982119-C-T

Variant summary

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

The NM_015380.5(SAMM50):​c.1007+658C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,026 control chromosomes in the GnomAD database, including 5,073 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 0.24 (5073 hom., cov: 32)
• Consequence: SAMM50 NM_015380.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173

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]

SAMM50 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• 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	Protein	UniProt
SAMM50	NM_015380.5	c.1007+658C>T		intron_variant		ENST00000350028.5	NP_056195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAMM50	ENST00000350028.5	c.1007+658C>T		intron_variant		1	NM_015380.5	ENSP00000345445.4
SAMM50	ENST00000474323.5	n.1819+658C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35912 AN: 151908 Hom.: 5067 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.236 AC: 35938 AN: 152026 Hom.: 5073 Cov.: 32 AF XY: 0.241 AC XY: 17891 AN XY: 74310

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.214

Alfa AF: 0.171 Hom.: 1228

Bravo AF: 0.249

Asia WGS AF: 0.277 AC: 961 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.87

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: rs2235776; hg19: chr22-44377999;