6-107040076-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The ENST00000311381.8(MTRES1):​c.316T>C​(p.Ser106Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MTRES1
ENST00000311381.8 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39
Variant links:
Genes affected
MTRES1 (HGNC:17971): (mitochondrial transcription rescue factor 1) Enables ribosomal large subunit binding activity and tRNA binding activity. Involved in regulation of mitochondrial transcription and rescue of stalled ribosome. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity MRES1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12786776).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MTRES1NM_016487.5 linkuse as main transcriptc.316T>C p.Ser106Pro missense_variant 2/4 ENST00000311381.8 NP_057571.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MTRES1ENST00000311381.8 linkuse as main transcriptc.316T>C p.Ser106Pro missense_variant 2/41 NM_016487.5 ENSP00000310951 P1
MTRES1ENST00000625458.1 linkuse as main transcriptc.331T>C p.Ser111Pro missense_variant 3/53 ENSP00000485698
MTRES1ENST00000405204.6 linkuse as main transcriptc.316T>C p.Ser106Pro missense_variant 2/42 ENSP00000384867 P1
MTRES1ENST00000489790.1 linkuse as main transcriptn.85T>C non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 10, 2021The c.331T>C (p.S111P) alteration is located in exon 3 (coding exon 2) of the C6orf203 gene. This alteration results from a T to C substitution at nucleotide position 331, causing the serine (S) at amino acid position 111 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;T;.
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.17
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.62
.;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.9
L;L;.
MutationTaster
Benign
0.67
D;D;N
PROVEAN
Uncertain
-2.5
N;N;.
REVEL
Benign
0.13
Sift
Benign
0.14
T;T;.
Sift4G
Benign
0.15
T;T;T
Polyphen
0.98
D;D;.
Vest4
0.16
MutPred
0.20
Loss of phosphorylation at S106 (P = 7e-04);Loss of phosphorylation at S106 (P = 7e-04);.;
MVP
0.35
ClinPred
0.95
D
GERP RS
4.9
Varity_R
0.19
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-107361280; API