22-42079913-A-C

Variant names:

• chr22-42079913-A-C
• rs1344733083
• NM_033318.5:c.145A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033318.5(SMDT1):​c.145A>C​(p.Ile49Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMDT1 NM_033318.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.12
• Publications: 0 publications found

Genes affected

SMDT1 (HGNC:25055): (single-pass membrane protein with aspartate rich tail 1) This gene encodes a core regulatory component of a calcium channel in the mitochondrial inner membrane. [provided by RefSeq, Apr 2017]

ENSG00000309045 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27278572).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033318.5. 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
	SMDT1	NM_033318.5	MANE Select	c.145A>C	p.Ile49Leu	missense	Exon 1 of 3	NP_201575.3
	SMDT1	NR_146715.2		n.206+8A>C		splice_region intron	N/A
	SMDT1	NR_146717.1		n.-36A>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMDT1	ENST00000331479.4	TSL:1 MANE Select	c.145A>C	p.Ile49Leu	missense	Exon 1 of 3	ENSP00000327467.3	Q9H4I9
	SMDT1	ENST00000484235.1	TSL:1	n.214A>C		non_coding_transcript_exon	Exon 1 of 2
	SMDT1	ENST00000924439.1		c.145A>C	p.Ile49Leu	missense	Exon 1 of 4	ENSP00000594498.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000254 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.17
Sift	Benign	0.038	D
Sift4G	Benign	0.089	T
Polyphen		0.51	P
Vest4		0.33
MVP		0.38
MPC		0.95
ClinPred		0.95	D
GERP RS		6.1
PromoterAI		0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.46
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1344733083; hg19: chr22-42475917;