chr6-151468702-C-A

Variant names:

• chr6-151468702-C-A
• rs1266945627
• NM_024573.3:c.918C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024573.3(DCPH1):​c.918C>A​(p.His306Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCPH1 NM_024573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.486
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035366863).

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.918C>A	p.His306Gln	missense	Exon 5 of 5	NP_078849.1	Q9H993
	DCPH1	NM_001286562.2		c.561C>A	p.His187Gln	missense	Exon 4 of 4	NP_001273491.1	F5GZY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMT1	ENST00000367294.4	TSL:1 MANE Select	c.918C>A	p.His306Gln	missense	Exon 5 of 5	ENSP00000356263.3	Q9H993
	ARMT1	ENST00000852535.1		c.948C>A	p.His316Gln	missense	Exon 5 of 5	ENSP00000522594.1
	ARMT1	ENST00000852534.1		c.924C>A	p.His308Gln	missense	Exon 5 of 5	ENSP00000522593.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251126 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00000137 AC: 2 AN: 1461768 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111920

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0070
DANN	Benign	0.52
DEOGEN2	Benign	0.00059	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.49
PROVEAN	Benign	0.030	N
REVEL	Benign	0.041
Sift	Benign	0.58	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.041
MutPred		0.35		Gain of methylation at K310 (P = 0.0637)
MVP		0.048
MPC		0.13
ClinPred		0.045	T
GERP RS		-12
Varity_R		0.14
gMVP		0.19
Mutation Taster		=92/8	polymorphism

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: rs1266945627; hg19: chr6-151789837;