22-43972861-C-T

Variant names:

• chr22-43972861-C-T
• rs932430
• NM_015380.5:c.430-10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015380.5(SAMM50):​c.430-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,539,410 control chromosomes in the GnomAD database, including 180,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26107 hom., cov: 31)
  • Exomes 𝑓: 0.49 (154253 hom.)
• Consequence: SAMM50 NM_015380.5 intron
• Scores: Splicing: ADA: 0.00001562
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.596
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-43972861-C-T is Benign according to our data. Variant chr22-43972861-C-T is described in ClinVar as Benign. ClinVar VariationId is 769164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 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.430-10C>T		intron	N/A	NP_056195.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAMM50	ENST00000350028.5	TSL:1 MANE Select	c.430-10C>T		intron	N/A	ENSP00000345445.4	Q9Y512
	SAMM50	ENST00000943220.1		c.430-10C>T		intron	N/A	ENSP00000613279.1
	SAMM50	ENST00000854677.1		c.430-10C>T		intron	N/A	ENSP00000524736.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 87338 AN: 150120 Hom.: 26062 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.432

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.526

GnomAD2 exomes AF: 0.506 AC: 103392 AN: 204356 AF XY: 0.502

Gnomad AFR exome AF: 0.673

Gnomad AMR exome AF: 0.480

Gnomad ASJ exome AF: 0.408

Gnomad EAS exome AF: 0.707

Gnomad FIN exome AF: 0.546

Gnomad NFE exome AF: 0.440

Gnomad OTH exome AF: 0.470

GnomAD4 exome AF: 0.491 AC: 681980 AN: 1389184 Hom.: 154253 Cov.: 35 AF XY: 0.494 AC XY: 341534 AN XY: 691296

African (AFR) AF: 0.692 AC: 20515 AN: 29662

American (AMR) AF: 0.504 AC: 15909 AN: 31582

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 10411 AN: 24592

East Asian (EAS) AF: 0.771 AC: 28831 AN: 37382

South Asian (SAS) AF: 0.632 AC: 47867 AN: 75710

European-Finnish (FIN) AF: 0.572 AC: 29761 AN: 52024

Middle Eastern (MID) AF: 0.415 AC: 2314 AN: 5570

European-Non Finnish (NFE) AF: 0.463 AC: 497464 AN: 1075296

Other (OTH) AF: 0.504 AC: 28908 AN: 57366

GnomAD4 genome AF: 0.582 AC: 87432 AN: 150226 Hom.: 26107 Cov.: 31 AF XY: 0.587 AC XY: 43057 AN XY: 73298

African (AFR) AF: 0.710 AC: 29049 AN: 40940

American (AMR) AF: 0.529 AC: 8002 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1602 AN: 3452

East Asian (EAS) AF: 0.827 AC: 4257 AN: 5150

South Asian (SAS) AF: 0.696 AC: 3326 AN: 4780

European-Finnish (FIN) AF: 0.602 AC: 6017 AN: 9988

Middle Eastern (MID) AF: 0.451 AC: 130 AN: 288

European-Non Finnish (NFE) AF: 0.496 AC: 33512 AN: 67508

Other (OTH) AF: 0.531 AC: 1103 AN: 2078

Alfa AF: 0.531 Hom.: 44864

Bravo AF: 0.582

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	-0.90
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		-0.60
Mutation Taster		=10/90	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0020
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: rs932430; hg19: chr22-44368741;