Variant 17-81823475-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_207368.5(MCRIP1):c.166C>T(p.Pro56Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000722 in 1,384,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

MCRIP1
NM_207368.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

MCRIP1 (HGNC:28007): (MAPK regulated corepressor interacting protein 1) Involved in regulation of epithelial to mesenchymal transition. Located in cytoplasmic stress granule and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MCRIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03030324).

BP6

Variant 17-81823475-G-A is Benign according to our data. Variant chr17-81823475-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2253978.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCRIP1	NM_207368.5 linkuse as main transcript	c.166C>T	p.Pro56Ser	missense_variant	4/5	ENST00000455127.7	NP_997251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCRIP1	ENST00000455127.7 linkuse as main transcript	c.166C>T	p.Pro56Ser	missense_variant	4/5	1	NM_207368.5	ENSP00000409009	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

141250

Hom.:

AF XY:

0.0000264

AC XY:

AN XY:

75720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000367

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000722

AC:

AN:

1384380

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

683144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.4

DANN

Benign

0.70

DEOGEN2

Benign

0.0051

T;T;T;T;T;T;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.61

T;.;.;.;.;T;T;T;.

M_CAP

Benign

0.0018

MetaRNN

Benign

0.030

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.31

.;N;.;.;N;.;.;.;.

REVEL

Benign

0.041

Sift

Benign

1.0

.;T;.;.;T;.;.;.;.

Sift4G

Benign

0.88

T;T;T;T;T;T;T;T;T

Polyphen

0.0

.;B;B;.;B;B;.;.;.

Vest4

0.047

MutPred

0.19

.;Gain of MoRF binding (P = 0.0569);Gain of MoRF binding (P = 0.0569);.;Gain of MoRF binding (P = 0.0569);Gain of MoRF binding (P = 0.0569);.;Gain of MoRF binding (P = 0.0569);.;

MVP

0.014

MPC

.;.;3.71968781554E-4;.;.;.;.;.;.

ClinPred

0.014

GERP RS

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.19

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