22-42079838-AGC-GGA

Variant names:

• chr22-42079838-AGC-GGA
• NM_033318.5:c.70_72delAGCinsGGA
• SMDT1 p.Ser24Gly

Variant summary

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

The NM_033318.5(SMDT1):​c.70_72delAGCinsGGA​(p.Ser24Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMDT1 NM_033318.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• 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.

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.70_72delAGCinsGGA	p.Ser24Gly	missense	N/A	NP_201575.3
	SMDT1	NR_146715.2		n.139_141delAGCinsGGA		non_coding_transcript_exon	Exon 1 of 3
	SMDT1	NR_146717.1		n.-111_-109delAGCinsGGA		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.70_72delAGCinsGGA	p.Ser24Gly	missense	N/A	ENSP00000327467.3	Q9H4I9
	SMDT1	ENST00000484235.1	TSL:1	n.139_141delAGCinsGGA		non_coding_transcript_exon	Exon 1 of 2
	SMDT1	ENST00000924439.1		c.70_72delAGCinsGGA	p.Ser24Gly	missense	N/A	ENSP00000594498.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-42475842;