Variant chrX-9027885-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_205849.3(FAM9B):c.475C>T(p.Arg159Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000538 in 1,207,570 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R159H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000054 ( 0 hom. 32 hem. )

Consequence

FAM9B
NM_205849.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.535

Variant links:

Genes affected

FAM9B (HGNC:18404): (family with sequence similarity 9 member B) 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]

FAM9B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044690907).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM9B	NM_205849.3 linkuse as main transcript	c.475C>T	p.Arg159Cys	missense_variant	7/9	ENST00000327220.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9B	ENST00000327220.10 linkuse as main transcript	c.475C>T	p.Arg159Cys	missense_variant	7/9	1	NM_205849.3	P1	Q8IZU0-1

Frequencies

GnomAD3 genomes

AF:

0.0000536

AC:

AN:

111860

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34058

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000739

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.000664

GnomAD3 exomes

AF:

0.0000928

AC:

AN:

183182

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

67680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000579

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000611

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000538

AC:

AN:

1095657

Hom.:

Cov.:

AF XY:

0.0000886

AC XY:

AN XY:

361297

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000611

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000262

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

AF:

0.0000536

AC:

AN:

111913

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34121

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000742

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.000655

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2023

The c.475C>T (p.R159C) alteration is located in exon 6 (coding exon 6) of the FAM9B gene. This alteration results from a C to T substitution at nucleotide position 475, causing the arginine (R) at amino acid position 159 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

.;T;T

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.62

T;T;.

M_CAP

Benign

0.0013

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.098

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.083

T;D;D

Polyphen

1.0

.;D;D

Vest4

0.13

MVP

0.38

MPC

0.39

ClinPred

0.31

GERP RS

-0.85

Varity_R

0.11

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

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