NM_001286555.3:c.285C>T

Variant names:

• chr6-348124-C-T
• rs56362282
• NM_001286555.3:c.285C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6 BP7

The NM_001286555.3(DUSP22):​c.285C>T​(p.Ser95Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,597,692 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.017 (0 hom., cov: 61)
  • Exomes 𝑓: 0.020 (1 hom.)
• Consequence: DUSP22 NM_001286555.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.05
• Publications: 5 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Variant has high frequency in the NFE (0.0215) population. However there is too low homozygotes in high coverage region: (expected more than 149, got 1).
• BP6: Variant 6-348124-C-T is Benign according to our data. Variant chr6-348124-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3037645.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP22	NM_001286555.3	MANE Select	c.285C>T	p.Ser95Ser	synonymous	Exon 6 of 7	NP_001273484.1	Q9NRW4-2
	DUSP22	NM_020185.6		c.285C>T	p.Ser95Ser	synonymous	Exon 6 of 8	NP_064570.1	Q9NRW4-1
	DUSP22	NR_104473.3		n.288C>T		non_coding_transcript_exon	Exon 5 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP22	ENST00000419235.7	TSL:2 MANE Select	c.285C>T	p.Ser95Ser	synonymous	Exon 6 of 7	ENSP00000397459.2	Q9NRW4-2
	DUSP22	ENST00000344450.9	TSL:1	c.285C>T	p.Ser95Ser	synonymous	Exon 6 of 8	ENSP00000345281.5	Q9NRW4-1
	DUSP22	ENST00000603296.5	TSL:3	c.156C>T	p.Ser52Ser	synonymous	Exon 6 of 6	ENSP00000474082.1	S4R3A4

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2514 AN: 151274 Hom.: 0 Cov.: 61

Gnomad AFR AF: 0.00379

Gnomad AMI AF: 0.0188

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.0164 AC: 4090 AN: 249176 AF XY: 0.0161

Gnomad AFR exome AF: 0.00283

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.0120

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0448

Gnomad NFE exome AF: 0.0214

Gnomad OTH exome AF: 0.0199

GnomAD4 exome AF: 0.0197 AC: 28422 AN: 1446300 Hom.: 1 Cov.: 36 AF XY: 0.0191 AC XY: 13732 AN XY: 719794

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

African (AFR) AF: 0.00308 AC: 103 AN: 33448

American (AMR) AF: 0.0110 AC: 491 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 328 AN: 25992

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39692

South Asian (SAS) AF: 0.00317 AC: 273 AN: 86126

European-Finnish (FIN) AF: 0.0447 AC: 2341 AN: 52420

Middle Eastern (MID) AF: 0.00942 AC: 54 AN: 5732

European-Non Finnish (NFE) AF: 0.0217 AC: 23884 AN: 1098470

Other (OTH) AF: 0.0157 AC: 943 AN: 59920

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0166 AC: 2516 AN: 151392 Hom.: 0 Cov.: 61 AF XY: 0.0173 AC XY: 1282 AN XY: 74014

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

African (AFR) AF: 0.00378 AC: 157 AN: 41540

American (AMR) AF: 0.0145 AC: 221 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4830

European-Finnish (FIN) AF: 0.0476 AC: 495 AN: 10402

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0224 AC: 1514 AN: 67482

Other (OTH) AF: 0.0209 AC: 44 AN: 2106

⚠️ 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: 0.0147 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DUSP22-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.7
DANN	Benign	0.84
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=276/24	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: rs56362282; hg19: chr6-348124;