Variant 12-49563037-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006337.5(MCRS1):c.769C>T(p.Leu257Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000604 in 1,589,902 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

MCRS1
NM_006337.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.78

Variant links:

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]

MCRS1 links:

Genome browser will be placed here

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 linkuse as main transcript	c.769C>T	p.Leu257Phe	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 linkuse as main transcript	c.769C>T	p.Leu257Phe	missense_variant	8/15	1	NM_006337.5	ENSP00000345358	P1	Q96EZ8-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000954

AC:

AN:

209714

Hom.:

AF XY:

0.00000886

AC XY:

AN XY:

112838

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000223

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000619

AC:

AN:

1437662

Hom.:

Cov.:

AF XY:

0.0000659

AC XY:

AN XY:

712868

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000765

Gnomad4 OTH exome

AF:

0.0000674

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000166

AC:

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

Mar 29, 2022

The c.808C>T (p.L270F) alteration is located in exon 7 (coding exon 7) of the MCRS1 gene. This alteration results from a C to T substitution at nucleotide position 808, causing the leucine (L) at amino acid position 270 to be replaced by a phenylalanine (F). 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

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

.;T;T;.;T

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

D;.;D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.67

D;D;D;D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.8

.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.3

D;D;D;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.011

D;D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D;.

Polyphen

1.0, 1.0, 1.0

.;D;D;D;D

Vest4

0.68

MVP

0.96

MPC

1.5

ClinPred

0.95

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.45

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over