9-125543111-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001006617.3(MAPKAP1):c.906G>A(p.Lys302=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0086 in 1,614,014 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (81 hom.)
• Consequence: MAPKAP1 NM_001006617.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.635

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 9-125543111-C-T is Benign according to our data. Variant chr9-125543111-C-T is described in ClinVar as [Benign]. Clinvar id is 770956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.635 with no splicing effect.
• BS2: High AC in GnomAd at 1017 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPKAP1	NM_001006617.3	c.906G>A	p.Lys302=	synonymous_variant	7/12	ENST00000265960.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPKAP1	ENST00000265960.8	c.906G>A	p.Lys302=	synonymous_variant	7/12	1	NM_001006617.3	P1

Frequencies

GnomAD3 genomes AF: 0.00668 AC: 1017 AN: 152216 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00999

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00636 AC: 1600 AN: 251406 Hom.: 16 AF XY: 0.00631 AC XY: 858 AN XY: 135874

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0126

Gnomad NFE exome AF: 0.0102

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00880 AC: 12858 AN: 1461680 Hom.: 81 Cov.: 30 AF XY: 0.00870 AC XY: 6328 AN XY: 727166

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.00245

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.0126

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.00750

GnomAD4 genome AF: 0.00668 AC: 1017 AN: 152334 Hom.: 11 Cov.: 32 AF XY: 0.00671 AC XY: 500 AN XY: 74486

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0155

Gnomad4 NFE AF: 0.0100

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00868 Hom.: 7

Bravo AF: 0.00559

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00840

EpiControl AF: 0.00853

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

Invitae

Jul 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	4.6
Dann	Benign	0.61

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: rs11542134; hg19: chr9-128305390;