22-42079806-C-G

Variant names:

• chr22-42079806-C-G
• rs752386703
• NM_033318.5:c.38C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033318.5(SMDT1):​c.38C>G​(p.Pro13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. P13L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMDT1 NM_033318.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06930855).

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.38C>G	p.Pro13Arg	missense	Exon 1 of 3	NP_201575.3
	SMDT1	NR_146715.2		n.107C>G		non_coding_transcript_exon	Exon 1 of 3
	SMDT1	NR_146717.1		n.-143C>G		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.38C>G	p.Pro13Arg	missense	Exon 1 of 3	ENSP00000327467.3	Q9H4I9
	SMDT1	ENST00000484235.1	TSL:1	n.107C>G		non_coding_transcript_exon	Exon 1 of 2
	SMDT1	ENST00000924439.1		c.38C>G	p.Pro13Arg	missense	Exon 1 of 4	ENSP00000594498.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.12
Sift	Benign	0.18	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.24		Gain of helix (P = 0.0128)
MVP		0.095
MPC		0.38
ClinPred		0.093	T
GERP RS		3.0
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Varity_R		0.075
gMVP		0.54
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs752386703; hg19: chr22-42475810;