1-168729036-T-C

Position:

• chr1-168729036-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001937.5(DPT):​c.139A>G​(p.Ser47Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPT NM_001937.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

Genes affected

DPT (HGNC:3011): (dermatopontin) Dermatopontin is an extracellular matrix protein with possible functions in cell-matrix interactions and matrix assembly. The protein is found in various tissues and many of its tyrosine residues are sulphated. Dermatopontin is postulated to modify the behavior of TGF-beta through interaction with decorin. [provided by RefSeq, Jul 2008]

ENSG00000285622 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30412328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPT	NM_001937.5	c.139A>G	p.Ser47Gly	missense_variant	1/4	ENST00000367817.4	NP_001928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPT	ENST00000367817.4	c.139A>G	p.Ser47Gly	missense_variant	1/4	1	NM_001937.5	ENSP00000356791.3
ENSG00000285622	ENST00000650631.1	n.705+4057A>G		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Mar 18, 2024

The c.139A>G (p.S47G) alteration is located in exon 1 (coding exon 1) of the DPT gene. This alteration results from a A to G substitution at nucleotide position 139, causing the serine (S) at amino acid position 47 to be replaced by a glycine (G). 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
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.050
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.087
Sift	Benign	0.081	T
Sift4G	Uncertain	0.051	T
Polyphen		0.030	B
Vest4		0.27
MutPred		0.33		Loss of sheet (P = 0.0817);
MVP		0.68
MPC		0.44
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.30
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-168698274;