Variant 14-55063321-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144578.4(MAPK1IP1L):c.722C>T(p.Pro241Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,450,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

MAPK1IP1L
NM_144578.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

Variant links:

Genes affected

MAPK1IP1L (HGNC:19840): (mitogen-activated protein kinase 1 interacting protein 1 like)

MAPK1IP1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20350581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPK1IP1L	NM_144578.4 linkuse as main transcript	c.722C>T	p.Pro241Leu	missense_variant	3/4	ENST00000395468.9	NP_653179.1
MAPK1IP1L	XM_011537362.3 linkuse as main transcript	c.728C>T	p.Pro243Leu	missense_variant	3/4		XP_011535664.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPK1IP1L	ENST00000395468.9 linkuse as main transcript	c.722C>T	p.Pro241Leu	missense_variant	3/4	1	NM_144578.4	ENSP00000378851	P1
MAPK1IP1L	ENST00000553976.1 linkuse as main transcript	n.371C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

243806

Hom.:

AF XY:

0.00000758

AC XY:

AN XY:

132008

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:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000910

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000827

AC:

AN:

1450620

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720722

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:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Aug 08, 2023

The c.722C>T (p.P241L) alteration is located in exon 3 (coding exon 2) of the MAPK1IP1L gene. This alteration results from a C to T substitution at nucleotide position 722, causing the proline (P) at amino acid position 241 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.025

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.3

D;.

REVEL

Benign

0.10

Sift

Benign

0.22

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.0080

B;B

Vest4

0.54

MutPred

0.29

Gain of catalytic residue at P241 (P = 4e-04);Gain of catalytic residue at P241 (P = 4e-04);

MVP

0.28

MPC

0.11

ClinPred

0.13

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.33

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