chr6-348223-C-T

Variant names:

• chr6-348223-C-T
• rs370002831
• NM_001286555.3:c.384C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001286555.3(DUSP22):​c.384C>T​(p.Asn128Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000537 in 1,613,700 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 61)
  • Exomes 𝑓: 0.00056 (0 hom.)
• Consequence: DUSP22 NM_001286555.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23
• Publications: 1 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00875622).
• BP6: Variant 6-348223-C-T is Benign according to our data. Variant chr6-348223-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3388479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.23 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.384C>T	p.Asn128Asn	synonymous	Exon 6 of 7	NP_001273484.1	Q9NRW4-2
	DUSP22	NM_020185.6		c.384C>T	p.Asn128Asn	synonymous	Exon 6 of 8	NP_064570.1	Q9NRW4-1
	DUSP22	NR_104473.3		n.387C>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.384C>T	p.Asn128Asn	synonymous	Exon 6 of 7	ENSP00000397459.2	Q9NRW4-2
	DUSP22	ENST00000344450.9	TSL:1	c.384C>T	p.Asn128Asn	synonymous	Exon 6 of 8	ENSP00000345281.5	Q9NRW4-1
	DUSP22	ENST00000603881.5	TSL:3	c.47C>T	p.Thr16Met	missense	Exon 4 of 4	ENSP00000474450.1	S4R3K1

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152280 Hom.: 0 Cov.: 61

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00789

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00103 AC: 258 AN: 251298 AF XY: 0.00152

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000560 AC: 818 AN: 1461304 Hom.: 0 Cov.: 35 AF XY: 0.000813 AC XY: 591 AN XY: 726822

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

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.00850 AC: 729 AN: 85748

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

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

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1111974

Other (OTH) AF: 0.000381 AC: 23 AN: 60366

⚠️ 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: 0.000315 AC: 48 AN: 152396 Hom.: 0 Cov.: 61 AF XY: 0.000510 AC XY: 38 AN XY: 74526

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

African (AFR) AF: 0.0000721 AC: 3 AN: 41604

American (AMR) AF: 0.0000653 AC: 1 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.00832 AC: 40 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2114

⚠️ 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: 0.000171 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00150 AC: 182

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely 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_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.68
Eigen	Benign	0.13
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.73	D
MetaRNN	Benign	0.0088	T
PhyloP100		2.2
MVP		0.66
ClinPred		0.057	T
GERP RS		3.1
Mutation Taster		=99/1	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: rs370002831; hg19: chr6-348223;