9-125444576-C-T

Variant names:

• chr9-125444576-C-T
• rs35549826
• NM_001006617.3:c.1368G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BS1 BS2

The NM_001006617.3(MAPKAP1):​c.1368G>A​(p.Thr456Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000861 in 1,613,468 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (10 hom.)
• Consequence: MAPKAP1 NM_001006617.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.777
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP6: Variant 9-125444576-C-T is Benign according to our data. Variant chr9-125444576-C-T is described in ClinVar as Benign. ClinVar VariationId is 790626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.777 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000492 (719/1461134) while in subpopulation AFR AF = 0.017 (569/33452). AF 95% confidence interval is 0.0159. There are 10 homozygotes in GnomAdExome4. There are 312 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 670 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006617.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAP1	NM_001006617.3	MANE Select	c.1368G>A	p.Thr456Thr	synonymous	Exon 11 of 12	NP_001006618.1	Q9BPZ7-1
	MAPKAP1	NM_024117.4		c.1260G>A	p.Thr420Thr	synonymous	Exon 10 of 11	NP_077022.1	Q9BPZ7-2
	MAPKAP1	NM_001006619.2		c.1227G>A	p.Thr409Thr	synonymous	Exon 10 of 11	NP_001006620.1	Q9BPZ7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPKAP1	ENST00000265960.8	TSL:1 MANE Select	c.1368G>A	p.Thr456Thr	synonymous	Exon 11 of 12	ENSP00000265960.3	Q9BPZ7-1
	MAPKAP1	ENST00000350766.7	TSL:1	c.1260G>A	p.Thr420Thr	synonymous	Exon 10 of 11	ENSP00000265961.5	Q9BPZ7-2
	MAPKAP1	ENST00000373511.6	TSL:1	c.1227G>A	p.Thr409Thr	synonymous	Exon 10 of 11	ENSP00000362610.2	Q9BPZ7-3

Frequencies

GnomAD3 genomes AF: 0.00439 AC: 668 AN: 152216 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00117 AC: 293 AN: 251046 AF XY: 0.000870

Gnomad AFR exome AF: 0.0164

Gnomad AMR exome AF: 0.000523

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000492 AC: 719 AN: 1461134 Hom.: 10 Cov.: 30 AF XY: 0.000429 AC XY: 312 AN XY: 726960

African (AFR) AF: 0.0170 AC: 569 AN: 33452

American (AMR) AF: 0.000874 AC: 39 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1111572

Other (OTH) AF: 0.00109 AC: 66 AN: 60348

GnomAD4 genome AF: 0.00440 AC: 670 AN: 152334 Hom.: 5 Cov.: 32 AF XY: 0.00422 AC XY: 314 AN XY: 74484

African (AFR) AF: 0.0150 AC: 622 AN: 41584

American (AMR) AF: 0.00281 AC: 43 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00226 Hom.: 3

Bravo AF: 0.00515

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.8
DANN	Benign	0.82
PhyloP100		-0.78
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs35549826; hg19: chr9-128206855; COSMIC: COSV56364455;