rs12198312

Variant names:

• chr6-323326-C-T
• rs12198312
• NM_001286555.3:c.138+11364C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001286555.3(DUSP22):​c.138+11364C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 148,832 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.083 (39 hom., cov: 60)
• Consequence: DUSP22 NM_001286555.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 4 publications found

Genes affected

DUSP22 (HGNC:16077): (dual specificity phosphatase 22) Enables non-membrane spanning protein tyrosine phosphatase activity and protein tyrosine kinase binding activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; negative regulation of focal adhesion assembly; and negative regulation of non-membrane spanning protein tyrosine kinase activity. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in plasma membrane. Part of cytoplasm; filamentous actin; and leading edge of lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286555.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP22	NM_001286555.3	MANE Select	c.138+11364C>T		intron	N/A	NP_001273484.1
	DUSP22	NM_020185.6		c.138+11364C>T		intron	N/A	NP_064570.1
	DUSP22	NR_104473.3		n.191+11364C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP22	ENST00000419235.7	TSL:2 MANE Select	c.138+11364C>T		intron	N/A	ENSP00000397459.2
	DUSP22	ENST00000344450.9	TSL:1	c.138+11364C>T		intron	N/A	ENSP00000345281.5
	DUSP22	ENST00000603453.5	TSL:4	c.-171-11788C>T		intron	N/A	ENSP00000474646.1

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12383 AN: 148716 Hom.: 39 Cov.: 60

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.0886

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.0777

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0786

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

GnomAD4 genome AF: 0.0834 AC: 12406 AN: 148832 Hom.: 39 Cov.: 60 AF XY: 0.0812 AC XY: 5909 AN XY: 72774

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0529 AC: 2158 AN: 40790

American (AMR) AF: 0.0735 AC: 1102 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.0777 AC: 266 AN: 3422

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5190

South Asian (SAS) AF: 0.0166 AC: 80 AN: 4812

European-Finnish (FIN) AF: 0.104 AC: 1069 AN: 10288

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7453 AN: 66068

Other (OTH) AF: 0.0826 AC: 172 AN: 2082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0986 Hom.: 46

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		0.33
Mutation Taster		=100/0	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: rs12198312; hg19: chr6-323326;