rs368803417

Variant names:

• chr19-4345820-C-A
• rs368803417
• NM_001300862.2:c.370C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-4345820-C-A
• chr19-4345820-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001300862.2(MPND):​c.370C>A​(p.Pro124Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P124S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPND NM_001300862.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.17

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPND	NM_001300862.2	c.370C>A	p.Pro124Thr	missense_variant	Exon 3 of 13	ENST00000599840.6	NP_001287791.1
MPND	NM_032868.6	c.370C>A	p.Pro124Thr	missense_variant	Exon 3 of 12		NP_116257.2
MPND	NM_001159846.3	c.370C>A	p.Pro124Thr	missense_variant	Exon 3 of 11		NP_001153318.1
MPND	XM_006722926.3	c.370C>A	p.Pro124Thr	missense_variant	Exon 3 of 13		XP_006722989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPND	ENST00000599840.6	c.370C>A	p.Pro124Thr	missense_variant	Exon 3 of 13	5	NM_001300862.2	ENSP00000471735.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.86	D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.7	M;M;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-7.9	D;D;.;.
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D;D;.;.
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.86
MutPred		0.49		Loss of glycosylation at P124 (P = 0.0601);Loss of glycosylation at P124 (P = 0.0601);Loss of glycosylation at P124 (P = 0.0601);.;
MVP		0.77
MPC		1.3
ClinPred		1.0	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.86
gMVP		0.79

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

LitVar

Other links and lift over

dbSNP: rs368803417; hg19: chr19-4345817;