NM_005792.2:c.401A>G

Variant names:

• chr16-82148813-T-C
• rs34375324
• NM_005792.2:c.401A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005792.2. 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
	MPHOSPH6	NM_005792.2	MANE Select	c.401A>G	p.Asp134Gly	missense	Exon 5 of 5	NP_005783.2	Q99547

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPHOSPH6	ENST00000258169.9	TSL:1 MANE Select	c.401A>G	p.Asp134Gly	missense	Exon 5 of 5	ENSP00000258169.4	Q99547
	MPHOSPH6	ENST00000953188.1		c.431A>G	p.Asp144Gly	missense	Exon 5 of 5	ENSP00000623247.1
	MPHOSPH6	ENST00000880962.1		c.419A>G	p.Asp140Gly	missense	Exon 5 of 5	ENSP00000551021.1

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

GnomAD2 exomes AF: 0.00923 AC: 2320 AN: 251450 AF XY: 0.00928

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 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

African (AFR) AF: 0.00260 AC: 87 AN: 33478

American (AMR) AF: 0.00662 AC: 296 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00842 AC: 220 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.00383 AC: 330 AN: 86258

European-Finnish (FIN) AF: 0.00330 AC: 176 AN: 53412

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.0185 AC: 20547 AN: 1111840

Other (OTH) AF: 0.0140 AC: 845 AN: 60390

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

African (AFR) AF: 0.00327 AC: 136 AN: 41550

American (AMR) AF: 0.00903 AC: 138 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4828

European-Finnish (FIN) AF: 0.00386 AC: 41 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0166 AC: 1128 AN: 68000

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.0138 Hom.: 59

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.095
Sift	Benign	0.032	D
Sift4G	Benign	0.15	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
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs34375324; hg19: chr16-82182418; COSMIC: COSV50736812; COSMIC: COSV50736812;