22-43972861-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015380.5(SAMM50):c.430-10C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001562
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.596

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 -14 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 id is 769164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAMM50	NM_015380.5	c.430-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000350028.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAMM50	ENST00000350028.5	c.430-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015380.5	P1
SAMM50	ENST00000493161.1	n.612-10C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.506 AC: 103392 AN: 204356 Hom.: 22253 AF XY: 0.502 AC XY: 56059 AN XY: 111780

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 SAS exome AF: 0.601

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

Gnomad4 AFR exome AF: 0.692

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.771

Gnomad4 SAS exome AF: 0.632

Gnomad4 FIN exome AF: 0.572

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.504

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

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.531

Alfa AF: 0.524 Hom.: 11085

Bravo AF: 0.582

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs932430; hg19: chr22-44368741;