Variant 9-125672553-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001006617.3(MAPKAP1):c.22A>G(p.Thr8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,614,200 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

MAPKAP1
NM_001006617.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

Variant links:

Genes affected

MAPKAP1 (HGNC:18752): (MAPK associated protein 1) This gene encodes a protein that is highly similar to the yeast SIN1 protein, a stress-activated protein kinase. Alternatively spliced transcript variants encoding distinct isoforms have been described. Alternate polyadenylation sites as well as alternate 3' UTRs have been identified for transcripts of this gene. [provided by RefSeq, Jul 2008]

MAPKAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028186679).

BS2

High AC in GnomAd4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAPKAP1	NM_001006617.3 linkuse as main transcript	c.22A>G	p.Thr8Ala	missense_variant	2/12	ENST00000265960.8	NP_001006618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAPKAP1	ENST00000265960.8 linkuse as main transcript	c.22A>G	p.Thr8Ala	missense_variant	2/12	1	NM_001006617.3	ENSP00000265960	P1	Q9BPZ7-1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000314

AC:

AN:

251356

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000222

AC:

325

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

173

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000276

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000282

Hom.:

Bravo

AF:

0.000397

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000354

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000474

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 28, 2022

The c.22A>G (p.T8A) alteration is located in exon 2 (coding exon 1) of the MAPKAP1 gene. This alteration results from a A to G substitution at nucleotide position 22, causing the threonine (T) at amino acid position 8 to be replaced by an alanine (A). 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

0.047

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.35

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

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

D;.;D;D;D;D;D

M_CAP

Benign

0.0011

MetaRNN

Benign

0.028

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.76

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

MutationTaster

Benign

0.71

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.19

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

REVEL

Benign

0.22

Sift

Benign

0.92

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

Sift4G

Benign

0.86

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

Polyphen

0.0

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

Vest4

0.12

MVP

0.35

MPC

0.73

ClinPred

0.0071

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.29

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