X-44844512-T-C

Variant names:

• chrX-44844512-T-C
• rs754915438
• NM_022076.4:c.380T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_022076.4(DUSP21):​c.380T>C​(p.Met127Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,098,210 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. 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. M127K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000010 (0 hom. 3 hem.)
• Consequence: DUSP21 NM_022076.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.93
• Publications: 0 publications found

Genes affected

DUSP21 (HGNC:20476): (dual specificity phosphatase 21) This gene encodes a member of the dual specificity phosphatase family, specifically the low molecular weight dual specificity phosphatase family. The encoded protein localizes to both the cytoplasm and the nucleus and functions to remove phosphate groups from phosphotyrosine and phosphothreonine residues.[provided by RefSeq, Mar 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022076.4. 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
	DUSP21	NM_022076.4	MANE Select	c.380T>C	p.Met127Thr	missense	Exon 1 of 1	NP_071359.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUSP21	ENST00000339042.6	TSL:6 MANE Select	c.380T>C	p.Met127Thr	missense	Exon 1 of 1	ENSP00000343244.4	Q9H596

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.0000219 AC: 4 AN: 183062 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000100 AC: 11 AN: 1098210 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 3 AN XY: 363564

African (AFR) AF: 0.00 AC: 0 AN: 26401

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.0000119 AC: 10 AN: 842120

Other (OTH) AF: 0.00 AC: 0 AN: 46096

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.82
DEOGEN2	Uncertain	0.66	D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.46	P
Vest4		0.41
MutPred		0.69		Loss of stability (P = 0.0667)
MVP		0.66
MPC		1.1
ClinPred		0.58	D
GERP RS		4.2
PromoterAI		0.011	Neutral
Varity_R		0.71
gMVP		0.94
Mutation Taster		=89/11	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: rs754915438; hg19: chrX-44703758;