Genetic Variant DCPH1:p.Ser272Cys (chr6-151468599-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024573.3(DCPH1):c.815C>G(p.Ser272Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DCPH1
NM_024573.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

Publications

0 publications found

Variant links:

Genes affected

DCPH1 (HGNC:17872): (acidic residue methyltransferase 1) Enables S-adenosylmethionine-dependent methyltransferase activity; enzyme binding activity; and protein carboxyl O-methyltransferase activity. Involved in methylation and regulation of response to DNA damage stimulus. [provided by Alliance of Genome Resources, Apr 2022]

DCPH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21225339).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024573.3. 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
	DCPH1	NM_024573.3	MANE Select	c.815C>G	p.Ser272Cys	missense	Exon 5 of 5	NP_078849.1	Q9H993
	DCPH1	NM_001286562.2		c.458C>G	p.Ser153Cys	missense	Exon 4 of 4	NP_001273491.1	F5GZY1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARMT1	ENST00000367294.4	TSL:1 MANE Select	c.815C>G	p.Ser272Cys	missense	Exon 5 of 5	ENSP00000356263.3	Q9H993
ARMT1	ENST00000852535.1		c.845C>G	p.Ser282Cys	missense	Exon 5 of 5	ENSP00000522594.1
ARMT1	ENST00000852534.1		c.821C>G	p.Ser274Cys	missense	Exon 5 of 5	ENSP00000522593.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251148

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111984

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0098

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.2

PhyloP100

4.1

PROVEAN

Benign

-1.7

REVEL

Benign

0.20

Sift

Benign

0.065

Sift4G

Benign

0.19

Polyphen

0.43

Vest4

0.44

MVP

0.62

MPC

0.19

ClinPred

0.36

GERP RS

6.0

Varity_R

0.51

gMVP

0.59

Mutation Taster

=69/31

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over