chr16-82148813-T-C

Position:

• chr16-82148813-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005792.2(MPHOSPH6):​c.401A>G​(p.Asp134Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0149 in 1,613,936 control chromosomes in the GnomAD database, including 234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (15 hom., cov: 32)
  • Exomes 𝑓: 0.015 (219 hom.)
• Consequence: MPHOSPH6 NM_005792.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.75

Genes affected

MPHOSPH6 (HGNC:7214): (M-phase phosphoprotein 6) Predicted to enable RNA binding activity. Involved in maturation of 5.8S rRNA. Located in cytosol; nucleolus; and nucleoplasm. Colocalizes with nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037452579).
• BP6: Variant 16-82148813-T-C is Benign according to our data. Variant chr16-82148813-T-C is described in ClinVar as [Benign]. Clinvar id is 780163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.01 (1522/152236) while in subpopulation NFE AF= 0.0166 (1128/68000). AF 95% confidence interval is 0.0158. There are 15 homozygotes in gnomad4. There are 651 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPHOSPH6	NM_005792.2	c.401A>G	p.Asp134Gly	missense_variant	5/5	ENST00000258169.9
MPHOSPH6	XM_011522808.4	c.347A>G	p.Asp116Gly	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPHOSPH6	ENST00000258169.9	c.401A>G	p.Asp134Gly	missense_variant	5/5	1	NM_005792.2	P1
MPHOSPH6	ENST00000563504.5	c.314A>G	p.Asp105Gly	missense_variant	5/5	2
MPHOSPH6	ENST00000563100.5	c.347A>G	p.Asp116Gly	missense_variant, NMD_transcript_variant	6/7	5

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1522 AN: 152118 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00904

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00923 AC: 2320 AN: 251450 Hom.: 16 AF XY: 0.00928 AC XY: 1261 AN XY: 135898

Gnomad AFR exome AF: 0.00308

Gnomad AMR exome AF: 0.00691

Gnomad ASJ exome AF: 0.00863

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00389

Gnomad FIN exome AF: 0.00282

Gnomad NFE exome AF: 0.0149

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.0154 AC: 22516 AN: 1461700 Hom.: 219 Cov.: 32 AF XY: 0.0150 AC XY: 10900 AN XY: 727160

Gnomad4 AFR exome AF: 0.00260

Gnomad4 AMR exome AF: 0.00662

Gnomad4 ASJ exome AF: 0.00842

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00383

Gnomad4 FIN exome AF: 0.00330

Gnomad4 NFE exome AF: 0.0185

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0100 AC: 1522 AN: 152236 Hom.: 15 Cov.: 32 AF XY: 0.00875 AC XY: 651 AN XY: 74438

Gnomad4 AFR AF: 0.00327

Gnomad4 AMR AF: 0.00903

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.0144 Hom.: 23

Bravo AF: 0.00995

TwinsUK AF: 0.0162 AC: 60

ALSPAC AF: 0.0202 AC: 78

ESP6500AA AF: 0.00386 AC: 17

ESP6500EA AF: 0.0155 AC: 133

ExAC AF: 0.00888 AC: 1078

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0161

EpiControl AF: 0.0157

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.74	T;T
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.9	D;N
REVEL	Benign	0.095
Sift	Benign	0.032	D;D
Sift4G	Benign	0.15	T;T
Polyphen		0.35	B;.
Vest4		0.41
MVP		0.49
MPC		0.0015
ClinPred		0.035	T
GERP RS		5.8
Varity_R		0.63
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34375324; hg19: chr16-82182418; COSMIC: COSV50736812; COSMIC: COSV50736812;