dbSNP rs1411016424: SMDT1:p.Ala6Asp (chr22-42079785-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_033318.5(SMDT1):c.17C>A(p.Ala6Asp) 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. 13/22 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. A6V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMDT1
NM_033318.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

0 publications found

Variant links:

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]

SMDT1 links:

ENSG00000309045 (HGNC:):

ENSG00000309045 links:

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ACMG classification

Classification was made for transcript

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=0.34473455).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SMDT1	NM_033318.5	MANE Select	c.17C>A	p.Ala6Asp	missense	Exon 1 of 3	NP_201575.3
SMDT1	NR_146715.2		n.86C>A		non_coding_transcript_exon	Exon 1 of 3
SMDT1	NR_146717.1		n.-164C>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMDT1	ENST00000331479.4	TSL:1 MANE Select	c.17C>A	p.Ala6Asp	missense	Exon 1 of 3	ENSP00000327467.3	Q9H4I9
SMDT1	ENST00000484235.1	TSL:1	n.86C>A		non_coding_transcript_exon	Exon 1 of 2
SMDT1	ENST00000924439.1		c.17C>A	p.Ala6Asp	missense	Exon 1 of 4	ENSP00000594498.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

237398

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454718

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723748

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

86160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110692

Other (OTH)

AF:

0.00

AC:

AN:

60090

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Benign

-0.028

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.59

M_CAP

Benign

0.020

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.5

PhyloP100

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.47

REVEL

Benign

0.14

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.013

Polyphen

0.0040

Vest4

0.61

MutPred

0.34

Loss of helix (P = 0.028)

MVP

0.32

MPC

0.72

ClinPred

0.96

GERP RS

5.2

PromoterAI

0.080

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

Varity_R

0.53

gMVP

0.74

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over