1-44220172-G-A

Position:

• chr1-44220172-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019100.5(DMAP1):​c.1207G>A​(p.Val403Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,562 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 (1 hom.)
• Consequence: DMAP1 NM_019100.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60

Genes affected

DMAP1 (HGNC:18291): (DNA methyltransferase 1 associated protein 1) This gene encodes a subunit of several, distinct complexes involved in the repression or activation of transcription. The encoded protein can independently repress transcription and is targeted to replication foci throughout S phase by interacting directly with the N-terminus of DNA methyltransferase 1. During late S phase, histone deacetylase 2 is added to this complex, providing a means to deacetylate histones in transcriptionally inactive heterochromatin following replication. The encoded protein is also a component of the nucleosome acetyltransferase of H4 complex and interacts with the transcriptional corepressor tumor susceptibility gene 101 and the pro-apoptotic death-associated protein 6, among others. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19707686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMAP1	NM_019100.5	c.1207G>A	p.Val403Met	missense_variant	9/10	ENST00000372289.7
DMAP1	NM_001034023.2	c.1207G>A	p.Val403Met	missense_variant	10/11
DMAP1	NM_001034024.2	c.1207G>A	p.Val403Met	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMAP1	ENST00000372289.7	c.1207G>A	p.Val403Met	missense_variant	9/10	1	NM_019100.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456562 Hom.: 1 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 723664

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.: 33

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

Sep 06, 2022

The c.1207G>A (p.V403M) alteration is located in exon 9 (coding exon 9) of the DMAP1 gene. This alteration results from a G to A substitution at nucleotide position 1207, causing the valine (V) at amino acid position 403 to be replaced by a methionine (M). 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	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T;T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.17	N;N;N
REVEL	Benign	0.088
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.27	B;B;B
Vest4		0.26
MutPred		0.62		Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);
MVP		0.46
MPC		0.92
ClinPred		0.27	T
GERP RS		4.4
Varity_R		0.044
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr1-44685844;