19-4343769-C-T

Variant names:

• chr19-4343769-C-T
• rs372519061
• NM_001300862.2:c.69C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001300862.2(MPND):​c.69C>T​(p.Asp23Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000946 in 1,057,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: MPND NM_001300862.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP7: Synonymous conserved (PhyloP=-0.135 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300862.2. 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
	MPND	NM_001300862.2	MANE Select	c.69C>T	p.Asp23Asp	synonymous	Exon 2 of 13	NP_001287791.1	W4VSR2
	MPND	NM_032868.6		c.69C>T	p.Asp23Asp	synonymous	Exon 2 of 12	NP_116257.2
	MPND	NM_001159846.3		c.69C>T	p.Asp23Asp	synonymous	Exon 2 of 11	NP_001153318.1	Q8N594-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPND	ENST00000599840.6	TSL:5 MANE Select	c.69C>T	p.Asp23Asp	synonymous	Exon 2 of 13	ENSP00000471735.1	W4VSR2
	MPND	ENST00000262966.12	TSL:1	c.69C>T	p.Asp23Asp	synonymous	Exon 2 of 12	ENSP00000262966.7	Q8N594-1
	MPND	ENST00000594716.5	TSL:1	n.69C>T		non_coding_transcript_exon	Exon 2 of 12	ENSP00000470987.1	M0R044

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.46e-7 AC: 1 AN: 1057564 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 500318

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21776

American (AMR) AF: 0.00 AC: 0 AN: 7456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12868

East Asian (EAS) AF: 0.00 AC: 0 AN: 23858

South Asian (SAS) AF: 0.00 AC: 0 AN: 19404

European-Finnish (FIN) AF: 0.0000429 AC: 1 AN: 23326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 904592

Other (OTH) AF: 0.00 AC: 0 AN: 41530

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Uncertain	0.98
PhyloP100		-0.14
PromoterAI		-0.089	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs372519061; hg19: chr19-4343766;