chr16-82170139-G-C

Variant names:

• chr16-82170139-G-C
• rs745539698
• NM_005792.2:c.37C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005792.2(MPHOSPH6):​c.37C>G​(p.Leu13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,441,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 37)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: MPHOSPH6 NM_005792.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0250
• Publications: 0 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]

MPHOSPH6-DT (HGNC:55377): (MPHOSPH6 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20825163).

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.37C>G	p.Leu13Val	missense	Exon 1 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.37C>G	p.Leu13Val	missense	Exon 1 of 5	ENSP00000258169.4	Q99547
	MPHOSPH6	ENST00000569021.1	TSL:1	c.37C>G	p.Leu13Val	missense	Exon 1 of 2	ENSP00000454900.1	H3BNK8
	MPHOSPH6	ENST00000563504.5	TSL:2	c.-50C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000456626.1	H3BSB3

Frequencies

GnomAD3 genomes Cov.: 37

GnomAD2 exomes AF: 0.0000354 AC: 8 AN: 226124 AF XY: 0.0000486

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000106

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000104 AC: 15 AN: 1441644 Hom.: 0 Cov.: 54 AF XY: 0.0000153 AC XY: 11 AN XY: 716928

African (AFR) AF: 0.00 AC: 0 AN: 32008

American (AMR) AF: 0.00 AC: 0 AN: 42532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25656

East Asian (EAS) AF: 0.00 AC: 0 AN: 37384

South Asian (SAS) AF: 0.000154 AC: 13 AN: 84180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102388

Other (OTH) AF: 0.0000336 AC: 2 AN: 59570

GnomAD4 genome Cov.: 37

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.025
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.16
Sift	Benign	0.041	D
Sift4G	Benign	0.29	T
Polyphen		0.20	B
Vest4		0.56
MutPred		0.67		Loss of helix (P = 0.0444)
MVP		0.27
MPC		0.0018
ClinPred		0.20	T
GERP RS		0.24
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.53
gMVP		0.43
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs745539698; hg19: chr16-82203744;