chr6-43229427-G-T

Position:

• chr6-43229427-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006443.3(DNPH1):​c.30C>A​(p.Ser10Arg) 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. 14/20 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNPH1 NM_006443.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.146

Genes affected

DNPH1 (HGNC:21218): (2'-deoxynucleoside 5'-phosphate N-hydrolase 1) This gene was identified on the basis of its stimulation by c-Myc protein. The latter is a transcription factor that participates in the regulation of cell proliferation, differentiation, and apoptosis. The exact function of this gene is not known but studies in rat suggest a role in cellular proliferation and c-Myc-mediated transformation. Two alternative transcripts encoding different proteins have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06226504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNPH1	NM_006443.3	c.30C>A	p.Ser10Arg	missense_variant	1/4	ENST00000230431.11	NP_006434.1
DNPH1	NM_199184.2	c.30C>A	p.Ser10Arg	missense_variant	1/3		NP_954653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNPH1	ENST00000230431.11	c.30C>A	p.Ser10Arg	missense_variant	1/4	1	NM_006443.3	ENSP00000230431.7
DNPH1	ENST00000509253.5	c.27C>A	p.Ser9Arg	missense_variant	1/4	3		ENSP00000422440.1
DNPH1	ENST00000393987.2	c.30C>A	p.Ser10Arg	missense_variant	1/3	2		ENSP00000377556.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1248132 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 609926

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.: 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

Jun 05, 2023

The c.30C>A (p.S10R) alteration is located in exon 1 (coding exon 1) of the DNPH1 gene. This alteration results from a C to A substitution at nucleotide position 30, causing the serine (S) at amino acid position 10 to be replaced by an arginine (R). 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	0.087
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.8
DANN	Benign	0.86
DEOGEN2	Benign	0.043	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.23	T;T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.38	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.46	T;D;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.16
MutPred		0.17		Loss of phosphorylation at S10 (P = 0.0094);.;Loss of phosphorylation at S10 (P = 0.0094);
MVP		0.10
MPC		0.42
ClinPred		0.036	T
GERP RS		2.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.070
gMVP		0.28

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: chr6-43197165;