6-348266-G-T

Variant names:

• chr6-348266-G-T
• rs147464089
• NM_001286555.3:c.427G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001286555.3(DUSP22):​c.427G>T​(p.Val143Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V143I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 61)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DUSP22 NM_001286555.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74
• Publications: 8 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41938472).

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.427G>T	p.Val143Phe	missense	Exon 6 of 7	NP_001273484.1	Q9NRW4-2
	DUSP22	NM_020185.6		c.427G>T	p.Val143Phe	missense	Exon 6 of 8	NP_064570.1	Q9NRW4-1
	DUSP22	NR_104473.3		n.430G>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.427G>T	p.Val143Phe	missense	Exon 6 of 7	ENSP00000397459.2	Q9NRW4-2
	DUSP22	ENST00000344450.9	TSL:1	c.427G>T	p.Val143Phe	missense	Exon 6 of 8	ENSP00000345281.5	Q9NRW4-1
	DUSP22	ENST00000603453.5	TSL:4	c.118G>T	p.Val40Phe	missense	Exon 5 of 6	ENSP00000474646.1	S4R3M1

Frequencies

GnomAD3 genomes Cov.: 61

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251282 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727230

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ 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 Cov.: 61

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.7
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.17
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.42		Loss of ubiquitination at K140 (P = 0.1083)
MVP		0.48
MPC		0.30
ClinPred		0.80	D
GERP RS		5.8
Varity_R		0.85
gMVP		0.53
Mutation Taster		=41/59	disease causing

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: rs147464089; hg19: chr6-348266;