dbSNP rs749791292: FAM9A:p.Glu248Gly (chrX-8795166-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174951.3(FAM9A):c.743A>G(p.Glu248Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,046,942 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.0000011 ( 0 hom. 0 hem. )

Consequence

FAM9A
NM_174951.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.08

Publications

0 publications found

Variant links:

Genes affected

FAM9A (HGNC:18403): (family with sequence similarity 9 member A) This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be a nuclear protein that is localized to the nucleolus, and has some similarity to a synaptonemal complex protein. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Aug 2011]

FAM9A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.08063474).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174951.3. 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
	FAM9A	NM_174951.3	MANE Select	c.743A>G	p.Glu248Gly	missense	Exon 7 of 10	NP_777611.1	Q8IZU1
	FAM9A	NM_001171186.1		c.743A>G	p.Glu248Gly	missense	Exon 7 of 10	NP_001164657.1	Q8IZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM9A	ENST00000381003.7	TSL:1 MANE Select	c.743A>G	p.Glu248Gly	missense	Exon 7 of 10	ENSP00000370391.3	Q8IZU1
	FAM9A	ENST00000543214.1	TSL:1	c.743A>G	p.Glu248Gly	missense	Exon 7 of 10	ENSP00000440163.1	Q8IZU1

Frequencies

GnomAD3 genomes

AF:

0.0000185

AC:

AN:

107871

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

116833

AF XY:

0.00

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

AF:

0.00000106

AC:

AN:

939071

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

261339

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23068

American (AMR)

AF:

0.00

AC:

AN:

29531

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17875

East Asian (EAS)

AF:

0.00

AC:

AN:

27621

South Asian (SAS)

AF:

0.00

AC:

AN:

46791

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32443

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3793

European-Non Finnish (NFE)

AF:

0.00000139

AC:

AN:

717155

Other (OTH)

AF:

0.00

AC:

AN:

40794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000185

AC:

AN:

107871

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

30717

show subpopulations

African (AFR)

AF:

0.0000676

AC:

AN:

29576

American (AMR)

AF:

0.00

AC:

AN:

9968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2594

East Asian (EAS)

AF:

0.00

AC:

AN:

3412

South Asian (SAS)

AF:

0.00

AC:

AN:

2315

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5667

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51990

Other (OTH)

AF:

0.00

AC:

AN:

1450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000178

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.34

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.19

M_CAP

Benign

0.00093

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

-2.1

PROVEAN

Benign

-1.6

REVEL

Benign

0.079

Sift

Benign

0.31

Sift4G

Uncertain

0.052

Polyphen

0.86

Vest4

0.13

MutPred

0.22

Loss of solvent accessibility (P = 0.0635)

MVP

0.20

MPC

0.061

ClinPred

0.15

GERP RS

-0.75

Varity_R

0.060

gMVP

0.033

Mutation Taster

=99/1

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over