dbSNP rs139758889: C9orf50:p.Asn192Ser (chr9-129619764-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_199350.4(C9orf50):c.575A>G(p.Asn192Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,613,656 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0036 ( 18 hom. )

Consequence

C9orf50
NM_199350.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41

Variant links:

Genes affected

C9orf50 (HGNC:23677): (chromosome 9 open reading frame 50)

C9orf50 links:

NTMT1 (HGNC:23373): (N-terminal Xaa-Pro-Lys N-methyltransferase 1) The METTL11A gene encodes an N-terminal methyltransferase for the RAN (MIM 601179) guanine nucleotide exchange factor regulator of chromosome condensation 1 (RCC1; MIM 179710). METTL11A enzyme alpha-N-methylates other protein targets such as SET (MIM 600960) and RB (MIM 180200).[supplied by OMIM, Nov 2010]

NTMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034188926).

BP6

Variant 9-129619764-T-C is Benign according to our data. Variant chr9-129619764-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2659571.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C9orf50	NM_199350.4 link	c.575A>G	p.Asn192Ser	missense_variant	Exon 2 of 7	ENST00000372478.5	NP_955382.3	Q5SZB4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C9orf50	ENST00000372478.5 link	c.575A>G	p.Asn192Ser	missense_variant	Exon 2 of 7	2	NM_199350.4	ENSP00000361556.4	Q5SZB4
C9orf50	ENST00000619117.1 link	c.-368+839A>G		intron_variant	Intron 1 of 4	1		ENSP00000480795.1	A0A087WX76
NTMT1	ENST00000372486.5 link	c.-55+10586T>C		intron_variant	Intron 1 of 3	5		ENSP00000361564.1	Q9BV86-1
C9orf50	ENST00000651030.1 link	n.322A>G		non_coding_transcript_exon_variant	Exon 2 of 6

Frequencies

GnomAD3 genomes

AF:

0.00315

AC:

478

AN:

151656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000849

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00605

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00251

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00439

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00324

AC:

815

AN:

251470

Hom.:

AF XY:

0.00335

AC XY:

455

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00384

Gnomad ASJ exome

AF:

0.00694

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00425

Gnomad OTH exome

AF:

0.00700

GnomAD4 exome

AF:

0.00364

AC:

5314

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

2588

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.00681

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00259

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00392

Gnomad4 OTH exome

AF:

0.00430

GnomAD4 genome

AF:

0.00315

AC:

478

AN:

151774

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

216

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.000846

Gnomad4 AMR

AF:

0.00604

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00251

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00439

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00346

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.00308

AC:

374

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

C9orf50: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.98

DANN

Benign

0.59

DEOGEN2

Benign

0.00093

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.46

PROVEAN

Benign

-1.0

REVEL

Benign

0.019

Sift

Benign

0.92

Sift4G

Benign

0.65

Polyphen

0.010

Vest4

0.063

MVP

0.014

MPC

0.53

ClinPred

0.00099

GERP RS

-6.2

Varity_R

0.030

gMVP

0.012

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over