20-31861540-C-G

Position:

• chr20-31861540-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080611.5(DUSP15):​c.571G>C​(p.Ala191Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DUSP15 NM_080611.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.600

Genes affected

DUSP15 (HGNC:16236): (dual specificity phosphatase 15) The protein encoded by this gene has both protein-tyrosine phophatase activity and serine/threonine-specific phosphatase activity, and therefore is known as a dual specificity phosphatase. This protein may function in the differentiation of oligodendrocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07776782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUSP15	NM_080611.5	c.571G>C	p.Ala191Pro	missense_variant	7/7	ENST00000339738.10	NP_542178.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUSP15	ENST00000339738.10	c.571G>C	p.Ala191Pro	missense_variant	7/7	1	NM_080611.5	ENSP00000341658.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1359362 Hom.: 0 Cov.: 52 AF XY: 0.00 AC XY: 0 AN XY: 670528

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.0000110 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.571G>C (p.A191P) alteration is located in exon 7 (coding exon 7) of the DUSP15 gene. This alteration results from a G to C substitution at nucleotide position 571, causing the alanine (A) at amino acid position 191 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.5
DANN	Benign	0.92
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.59	T;.;.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.078	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.012
Sift	Uncertain	0.0080	D;D;D;D;D
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.047	.;.;.;.;B
Vest4		0.20
MutPred		0.25		.;.;.;.;Loss of helix (P = 0.0104);
MVP		0.10
MPC		0.28
ClinPred		0.19	T
GERP RS		-4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs781549982; hg19: chr20-30449343;