Variant X-9029399-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_205849.3(FAM9B):c.301C>T(p.His101Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,197,520 control chromosomes in the GnomAD database, including 67 homozygotes. There are 3,749 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 4 hom., 234 hem., cov: 23)

Exomes 𝑓: 0.011 ( 63 hom. 3515 hem. )

Consequence

FAM9B
NM_205849.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.364

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007429242).

BP6

Variant X-9029399-G-A is Benign according to our data. Variant chrX-9029399-G-A is described in ClinVar as [Benign]. Clinvar id is 720805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-9029399-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes 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.301C>T	p.His101Tyr	missense_variant	6/9	ENST00000327220.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9B	ENST00000327220.10 linkuse as main transcript	c.301C>T	p.His101Tyr	missense_variant	6/9	1	NM_205849.3	P1	Q8IZU0-1

Frequencies

GnomAD3 genomes

AF:

0.00770

AC:

861

AN:

111870

Hom.:

Cov.:

AF XY:

0.00687

AC XY:

234

AN XY:

34044

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00496

Gnomad ASJ

AF:

0.0128

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00148

Gnomad FIN

AF:

0.00398

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.00730

GnomAD3 exomes

AF:

0.00677

AC:

1216

AN:

179692

Hom.:

AF XY:

0.00639

AC XY:

419

AN XY:

65550

show subpopulations

Gnomad AFR exome

AF:

0.000917

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00198

Gnomad FIN exome

AF:

0.00384

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.00739

GnomAD4 exome

AF:

0.0106

AC:

11478

AN:

1085596

Hom.:

Cov.:

AF XY:

0.00999

AC XY:

3515

AN XY:

351764

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00256

Gnomad4 ASJ exome

AF:

0.0173

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00229

Gnomad4 FIN exome

AF:

0.00485

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.00970

GnomAD4 genome

AF:

0.00768

AC:

860

AN:

111924

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

234

AN XY:

34108

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.00496

Gnomad4 ASJ

AF:

0.0128

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00148

Gnomad4 FIN

AF:

0.00398

Gnomad4 NFE

AF:

0.0130

Gnomad4 OTH

AF:

0.00721

Alfa

AF:

0.0117

Hom.:

505

Bravo

AF:

0.00725

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0142

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.0125

AC:

ExAC

AF:

0.00660

AC:

801

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.3

DANN

Benign

0.42

DEOGEN2

Benign

0.0092

.;T;T

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.54

T;T;.

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.28

.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.56

N;N;N

REVEL

Benign

0.26

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.87

T;T;T

Polyphen

0.81

.;P;P

Vest4

0.055

MVP

0.35

MPC

0.36

ClinPred

0.024

GERP RS

-0.55

Varity_R

0.14

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