1-168714238-C-G

Variant names:

• chr1-168714238-C-G
• rs35449613
• NM_001937.5:c.414G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001937.5(DPT):​c.414G>C​(p.Arg138Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R138R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPT NM_001937.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 5 publications found

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]

LINC00970 (HGNC:48730): (long intergenic non-protein coding RNA 970)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001937.5. 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
	DPT	NM_001937.5	MANE Select	c.414G>C	p.Arg138Ser	missense	Exon 2 of 4	NP_001928.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPT	ENST00000367817.4	TSL:1 MANE Select	c.414G>C	p.Arg138Ser	missense	Exon 2 of 4	ENSP00000356791.3	Q07507
	DPT	ENST00000953565.1		c.414G>C	p.Arg138Ser	missense	Exon 2 of 5	ENSP00000623624.1
	DPT	ENST00000886480.1		c.414G>C	p.Arg138Ser	missense	Exon 2 of 3	ENSP00000556539.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.23
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.36	N
REVEL	Uncertain	0.30
Sift	Benign	0.48	T
Sift4G	Uncertain	0.045	D
Polyphen		0.99	D
Vest4		0.69
MutPred		0.48		Loss of catalytic residue at R138 (P = 0.0654)
MVP		0.57
MPC		0.40
ClinPred		0.90	D
GERP RS		-1.8
Varity_R		0.16
gMVP		0.71
Mutation Taster		=16/84	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: rs35449613; hg19: chr1-168683476;