chr19-4345946-C-T

Variant names:

• chr19-4345946-C-T
• NM_001300862.2:c.496C>T

Variant summary

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

The NM_001300862.2(MPND):​c.496C>T​(p.His166Tyr) 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. 15/21 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)
• Consequence: MPND NM_001300862.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

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=0.10569686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPND	NM_001300862.2	c.496C>T	p.His166Tyr	missense_variant	Exon 3 of 13	ENST00000599840.6	NP_001287791.1
MPND	NM_032868.6	c.496C>T	p.His166Tyr	missense_variant	Exon 3 of 12		NP_116257.2
MPND	NM_001159846.3	c.496C>T	p.His166Tyr	missense_variant	Exon 3 of 11		NP_001153318.1
MPND	XM_006722926.3	c.496C>T	p.His166Tyr	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.496C>T	p.His166Tyr	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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.496C>T (p.H166Y) alteration is located in exon 3 (coding exon 3) of the MPND gene. This alteration results from a C to T substitution at nucleotide position 496, causing the histidine (H) at amino acid position 166 to be replaced by a tyrosine (Y). 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.50
DEOGEN2	Benign	0.0086	T;.;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L;L;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N;N;.;.
REVEL	Benign	0.057
Sift	Benign	0.60	T;T;.;.
Sift4G	Benign	0.24	T;T;T;T
Polyphen		0.0080	B;B;.;.
Vest4		0.27
MutPred		0.30		Loss of disorder (P = 0.0615);Loss of disorder (P = 0.0615);Loss of disorder (P = 0.0615);.;
MVP		0.43
MPC		0.49
ClinPred		0.16	T
GERP RS		3.2
Varity_R		0.045
gMVP		0.26

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: chr19-4345943;