10-110503272-C-T

Variant names:

• chr10-110503272-C-T
• rs1889568
• NM_004419.4:c.528+403C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004419.4(DUSP5):​c.528+403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,086 control chromosomes in the GnomAD database, including 32,236 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32236 hom., cov: 33)
• Consequence: DUSP5 NM_004419.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893
• Publications: 8 publications found

Genes affected

DUSP5 (HGNC:3071): (dual specificity phosphatase 5) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, is expressed in a variety of tissues with the highest levels in pancreas and brain, and is localized in the nucleus. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUSP5	NM_004419.4	c.528+403C>T		intron_variant	Intron 2 of 3	ENST00000369583.4	NP_004410.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUSP5	ENST00000369583.4	c.528+403C>T		intron_variant	Intron 2 of 3	1	NM_004419.4	ENSP00000358596.3
DUSP5	ENST00000468749.1	n.124-161C>T		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98565 AN: 151968 Hom.: 32234 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.636

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.648 AC: 98601 AN: 152086 Hom.: 32236 Cov.: 33 AF XY: 0.652 AC XY: 48478 AN XY: 74360

African (AFR) AF: 0.584 AC: 24223 AN: 41476

American (AMR) AF: 0.660 AC: 10075 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2609 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3092 AN: 5180

South Asian (SAS) AF: 0.741 AC: 3575 AN: 4826

European-Finnish (FIN) AF: 0.711 AC: 7514 AN: 10570

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45290 AN: 67974

Other (OTH) AF: 0.634 AC: 1337 AN: 2110

Alfa AF: 0.664 Hom.: 56083

Bravo AF: 0.643

Asia WGS AF: 0.667 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.64
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1889568; hg19: chr10-112263030;