6-335143-G-A

Variant names:

• chr6-335143-G-A
• rs372273804
• NM_001286555.3:c.168G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001286555.3(DUSP22):​c.168G>A​(p.Ala56Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,613,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 64)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: DUSP22 NM_001286555.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.91
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-335143-G-A is Benign according to our data. Variant chr6-335143-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3054593.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.91 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.168G>A	p.Ala56Ala	synonymous	Exon 4 of 7	NP_001273484.1	Q9NRW4-2
	DUSP22	NM_020185.6		c.168G>A	p.Ala56Ala	synonymous	Exon 4 of 8	NP_064570.1	Q9NRW4-1
	DUSP22	NR_104474.3		n.138G>A		non_coding_transcript_exon	Exon 3 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP22	ENST00000419235.7	TSL:2 MANE Select	c.168G>A	p.Ala56Ala	synonymous	Exon 4 of 7	ENSP00000397459.2	Q9NRW4-2
	DUSP22	ENST00000344450.9	TSL:1	c.168G>A	p.Ala56Ala	synonymous	Exon 4 of 8	ENSP00000345281.5	Q9NRW4-1
	DUSP22	ENST00000603296.5	TSL:3	c.39G>A	p.Ala13Ala	synonymous	Exon 4 of 6	ENSP00000474082.1	S4R3A4

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152286 Hom.: 0 Cov.: 64

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251286 AF XY: 0.0000442

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000602 AC: 88 AN: 1461212 Hom.: 0 Cov.: 30 AF XY: 0.0000592 AC XY: 43 AN XY: 726942

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

African (AFR) AF: 0.0000896 AC: 3 AN: 33468

American (AMR) AF: 0.000112 AC: 5 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000460 AC: 12 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111496

Other (OTH) AF: 0.000149 AC: 9 AN: 60360

⚠️ 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: 0.000164 AC: 25 AN: 152286 Hom.: 0 Cov.: 64 AF XY: 0.000148 AC XY: 11 AN XY: 74400

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

African (AFR) AF: 0.000169 AC: 7 AN: 41482

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ 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: 0.000237 Hom.: 0

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	-0.52
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		-1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs372273804; hg19: chr6-335143; COSMIC: COSV60523662; COSMIC: COSV60523662;