Genetic Variant FAM9C:p.Arg113Gly (chrX-13039909-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_174901.6(FAM9C):c.337C>G(p.Arg113Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R113H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

FAM9C
NM_174901.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.02

Publications

0 publications found

Variant links:

Genes affected

FAM9C (HGNC:18405): (family with sequence similarity 9 member C) This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be localized to the nucleus as the protein contains several nuclear localization signals, and has similarity to a synaptonemal complex protein. [provided by RefSeq, Aug 2011]

FAM9C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174901.6. 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
	FAM9C	NM_174901.6	MANE Select	c.337C>G	p.Arg113Gly	missense	Exon 6 of 8	NP_777561.1	Q8IZT9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM9C	ENST00000380625.8	TSL:1 MANE Select	c.337C>G	p.Arg113Gly	missense	Exon 6 of 8	ENSP00000369999.3	Q8IZT9
FAM9C	ENST00000333995.7	TSL:1	c.337C>G	p.Arg113Gly	missense	Exon 6 of 7	ENSP00000334430.3	Q8IZT9
FAM9C	ENST00000542843.5	TSL:1	c.*2273C>G		3_prime_UTR	Exon 5 of 6	ENSP00000439185.1	G3V1I3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000585

AC:

AN:

170820

AF XY:

0.0000178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

9.21e-7

AC:

AN:

1085679

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

352073

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26032

American (AMR)

AF:

0.00

AC:

AN:

34013

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18924

East Asian (EAS)

AF:

0.00

AC:

AN:

29898

South Asian (SAS)

AF:

0.0000192

AC:

AN:

51994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4073

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

834882

Other (OTH)

AF:

0.00

AC:

AN:

45599

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.23

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.74

M_CAP

Benign

0.0021

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

2.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.098

Sift

Benign

0.087

Sift4G

Pathogenic

0.0

Polyphen

0.90

Vest4

0.13

MutPred

0.28

Loss of MoRF binding (P = 0.0453)

MVP

0.75

MPC

0.028

ClinPred

0.30

GERP RS

0.85

Varity_R

0.29

gMVP

0.11

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over