6-151464541-C-T

Variant names:

• chr6-151464541-C-T
• rs1781492824
• NM_024573.3:c.481C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_024573.3(DCPH1):​c.481C>T​(p.His161Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,114 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DCPH1 NM_024573.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0660
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052342355).
• BP6: Variant 6-151464541-C-T is Benign according to our data. Variant chr6-151464541-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3431421.Status of the report is criteria_provided_single_submitter, 1 stars.

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.481C>T	p.His161Tyr	missense	Exon 4 of 5	NP_078849.1	Q9H993
	DCPH1	NM_001286562.2		c.124C>T	p.His42Tyr	missense	Exon 3 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.481C>T	p.His161Tyr	missense	Exon 4 of 5	ENSP00000356263.3	Q9H993
	ARMT1	ENST00000852535.1		c.481C>T	p.His161Tyr	missense	Exon 4 of 5	ENSP00000522594.1
	ARMT1	ENST00000852534.1		c.481C>T	p.His161Tyr	missense	Exon 4 of 5	ENSP00000522593.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459114 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725936

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39540

South Asian (SAS) AF: 0.00 AC: 0 AN: 85888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110322

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.064
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.014
DANN	Benign	0.23
DEOGEN2	Benign	0.00097	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.91	T
PhyloP100		0.066
PROVEAN	Benign	2.4	N
REVEL	Benign	0.051
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.51		Loss of catalytic residue at H161 (P = 0.1783)
MVP		0.12
MPC		0.15
ClinPred		0.037	T
GERP RS		-2.3
Varity_R		0.042
gMVP		0.38
Mutation Taster		=88/12	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: rs1781492824; hg19: chr6-151785676; COSMIC: COSV66178479;