9-125644709-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001006617.3(MAPKAP1):c.498+12942C>G variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,964 control chromosomes in the GnomAD database, including 16,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (16416 hom., cov: 32)
• Consequence: MAPKAP1 NM_001006617.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.52

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 9-125644709-G-C is Benign according to our data. Variant chr9-125644709-G-C is described in ClinVar as [Benign]. Clinvar id is 1277692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPKAP1	NM_001006617.3	c.498+12942C>G		intron_variant		ENST00000265960.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPKAP1	ENST00000265960.8	c.498+12942C>G		intron_variant		1	NM_001006617.3	P1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67197 AN: 151846 Hom.: 16413 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.457

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.442 AC: 67212 AN: 151964 Hom.: 16416 Cov.: 32 AF XY: 0.445 AC XY: 33090 AN XY: 74284

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.456

Alfa AF: 0.479 Hom.: 2334

Bravo AF: 0.431

Asia WGS AF: 0.483 AC: 1679 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 29, 2020

This variant is associated with the following publications: (PMID: 31773361) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	24
Dann	Benign	0.84

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

Other links and lift over

dbSNP: rs473426; hg19: chr9-128406988;