12-49563027-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006337.5(MCRS1):c.779A>T(p.Gln260Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,442,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000049 ( 0 hom. )
Consequence
MCRS1
NM_006337.5 missense
NM_006337.5 missense
Scores
5
11
3
Clinical Significance
Conservation
PhyloP100: 7.80
Genes affected
MCRS1 (HGNC:6960): (microspherule protein 1) Enables RNA binding activity and telomerase inhibitor activity. Involved in histone H4 acetylation; negative regulation of DNA metabolic process; and positive regulation of protein localization to nucleolus. Located in cytoplasm; nucleolus; and nucleoplasm. Part of Ino80 complex; MLL1 complex; and histone acetyltransferase complex. [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.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MCRS1 | NM_006337.5 | c.779A>T | p.Gln260Leu | missense_variant | 8/15 | ENST00000343810.9 | NP_006328.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MCRS1 | ENST00000343810.9 | c.779A>T | p.Gln260Leu | missense_variant | 8/15 | 1 | NM_006337.5 | ENSP00000345358 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000904 AC: 2AN: 221228Hom.: 0 AF XY: 0.00000839 AC XY: 1AN XY: 119176
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GnomAD4 exome AF: 0.00000485 AC: 7AN: 1442882Hom.: 0 Cov.: 31 AF XY: 0.00000838 AC XY: 6AN XY: 715880
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ExAC
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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 submitter | clinical testing | Ambry Genetics | May 03, 2023 | The c.818A>T (p.Q273L) alteration is located in exon 7 (coding exon 7) of the MCRS1 gene. This alteration results from a A to T substitution at nucleotide position 818, causing the glutamine (Q) at amino acid position 273 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;.
Polyphen
0.065, 0.84, 0.94
.;B;B;P;P
Vest4
MutPred
0.43
.;Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);.;.;
MVP
MPC
1.0
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at