19-4343951-C-A

Position:

• chr19-4343951-C-A

Variant summary

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

The NM_001300862.2(MPND):​c.251C>A​(p.Ala84Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MPND NM_001300862.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

Genes affected

MPND (HGNC:25934): (MPN domain containing) Predicted to enable histone binding activity; peptidase activity; and transcription coactivator activity. Predicted to be involved in chromatin remodeling and positive regulation of transcription by RNA polymerase II. [provided by Alliance of Genome Resources, Apr 2022]

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=0.16041037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPND	NM_001300862.2	c.251C>A	p.Ala84Glu	missense_variant	2/13	ENST00000599840.6	NP_001287791.1
MPND	NM_032868.6	c.251C>A	p.Ala84Glu	missense_variant	2/12		NP_116257.2
MPND	NM_001159846.3	c.251C>A	p.Ala84Glu	missense_variant	2/11		NP_001153318.1
MPND	XM_006722926.3	c.251C>A	p.Ala84Glu	missense_variant	2/13		XP_006722989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPND	ENST00000599840.6	c.251C>A	p.Ala84Glu	missense_variant	2/13	5	NM_001300862.2	ENSP00000471735.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1231826 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 605770

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.: 32

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

Apr 05, 2023

The c.251C>A (p.A84E) alteration is located in exon 2 (coding exon 2) of the MPND gene. This alteration results from a C to A substitution at nucleotide position 251, causing the alanine (A) at amino acid position 84 to be replaced by a glutamic acid (E). 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	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0068	T;.;.;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	N;N;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.55	N;N;.;.
REVEL	Benign	0.057
Sift	Benign	0.24	T;T;.;.
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.018	B;B;.;.
Vest4		0.12
MutPred		0.52		Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);.;
MVP		0.28
MPC		2.1
ClinPred		0.56	D
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.10
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4343948;