13-19646979-G-A

Variant names:

• chr13-19646979-G-A
• rs376037584
• NM_017520.4:c.906G>A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_017520.4(MPHOSPH8):​c.906G>A​(p.Gln302Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000891 in 1,594,432 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (11 hom.)
• Consequence: MPHOSPH8 NM_017520.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.259

Genes affected

MPHOSPH8 (HGNC:29810): (M-phase phosphoprotein 8) Enables chromatin binding activity and methylated histone binding activity. Involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; regulation of DNA methylation; and regulation of gene expression. Located in several cellular components, including cytosol; heterochromatin; and nuclear lumen. Part of nucleosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-19646979-G-A is Benign according to our data. Variant chr13-19646979-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.259 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPHOSPH8	NM_017520.4	c.906G>A	p.Gln302Gln	synonymous_variant	Exon 3 of 14	ENST00000361479.10	NP_059990.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPHOSPH8	ENST00000361479.10	c.906G>A	p.Gln302Gln	synonymous_variant	Exon 3 of 14	1	NM_017520.4	ENSP00000355388.4
MPHOSPH8	ENST00000414242.3	c.225G>A	p.Gln75Gln	synonymous_variant	Exon 1 of 3	1		ENSP00000414663.3

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00142 AC: 329 AN: 231296 Hom.: 6 AF XY: 0.00169 AC XY: 212 AN XY: 125366

Gnomad AFR exome AF: 0.0000632

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.000468

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00719

Gnomad FIN exome AF: 0.0000476

Gnomad NFE exome AF: 0.000686

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.000926 AC: 1335 AN: 1442194 Hom.: 11 Cov.: 31 AF XY: 0.00115 AC XY: 827 AN XY: 717402

Gnomad4 AFR exome AF: 0.0000314

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.000442

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00728

Gnomad4 FIN exome AF: 0.0000565

Gnomad4 NFE exome AF: 0.000535

Gnomad4 OTH exome AF: 0.000994

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.000698 AC XY: 52 AN XY: 74448

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000538 Hom.: 1

Bravo AF: 0.000438

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MPHOSPH8: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.35
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

Publications

LitVar

Other links and lift over

dbSNP: rs376037584; hg19: chr13-20221119;