chr6-151468720-G-T

Variant names:

• chr6-151468720-G-T
• rs922691606
• NM_024573.3:c.936G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024573.3(DCPH1):​c.936G>T​(p.Met312Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,812 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: DCPH1 NM_024573.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80
• 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: 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=0.09449124).

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.936G>T	p.Met312Ile	missense	Exon 5 of 5	NP_078849.1	Q9H993
	DCPH1	NM_001286562.2		c.579G>T	p.Met193Ile	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.936G>T	p.Met312Ile	missense	Exon 5 of 5	ENSP00000356263.3	Q9H993
	ARMT1	ENST00000852535.1		c.966G>T	p.Met322Ile	missense	Exon 5 of 5	ENSP00000522594.1
	ARMT1	ENST00000852534.1		c.942G>T	p.Met314Ile	missense	Exon 5 of 5	ENSP00000522593.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461812 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727204

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

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111964

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.87
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.92	T
PhyloP100		2.8
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.027
Sift	Benign	0.26	T
Sift4G	Benign	0.60	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.66		Loss of ubiquitination at K314 (P = 0.0537)
MVP		0.11
MPC		0.15
ClinPred		0.35	T
GERP RS		3.5
Varity_R		0.14
gMVP		0.55
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: rs922691606; hg19: chr6-151789855;