22-43972242-A-T

Variant names:

• chr22-43972242-A-T
• rs3761472
• NM_015380.5:c.329A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015380.5(SAMM50):​c.329A>T​(p.Asp110Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D110G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAMM50 NM_015380.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAMM50	NM_015380.5	c.329A>T	p.Asp110Val	missense_variant	Exon 5 of 15	ENST00000350028.5	NP_056195.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAMM50	ENST00000350028.5	c.329A>T	p.Asp110Val	missense_variant	Exon 5 of 15	1	NM_015380.5	ENSP00000345445.4
SAMM50	ENST00000493161.1	n.511A>T		non_coding_transcript_exon_variant	Exon 5 of 7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.29
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.022	D
Polyphen		0.96	D
Vest4		0.53
MutPred		0.49		Gain of sheet (P = 0.1208);
MVP		0.74
MPC		0.61
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.36
gMVP		0.66

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: rs3761472; hg19: chr22-44368122;