Variant X-9032159-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.152C>T(p.Ala51Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000749 in 1,201,943 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 34 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000075 ( 0 hom. 32 hem. )

Consequence

FAM9B
NM_205849.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.23

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=0.012106448).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM9B	NM_205849.3 linkuse as main transcript	c.152C>T	p.Ala51Val	missense_variant, splice_region_variant	4/9	ENST00000327220.10
FAM9B	XM_047441882.1 linkuse as main transcript	c.287C>T	p.Ala96Val	missense_variant, splice_region_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9B	ENST00000327220.10 linkuse as main transcript	c.152C>T	p.Ala51Val	missense_variant, splice_region_variant	4/9	1	NM_205849.3	P1	Q8IZU0-1

Frequencies

GnomAD3 genomes

AF:

0.0000718

AC:

AN:

111480

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33748

show subpopulations

Gnomad AFR

AF:

0.0000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000942

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000918

AC:

AN:

174236

Hom.:

AF XY:

0.0000660

AC XY:

AN XY:

60604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00113

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000752

AC:

AN:

1090411

Hom.:

Cov.:

AF XY:

0.0000896

AC XY:

AN XY:

357201

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000811

Gnomad4 OTH exome

AF:

0.0000875

GnomAD4 genome

AF:

0.0000717

AC:

AN:

111532

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

33810

show subpopulations

Gnomad4 AFR

AF:

0.0000652

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000279

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000942

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ExAC

AF:

0.0000989

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

Jul 25, 2023

The c.152C>T (p.A51V) alteration is located in exon 3 (coding exon 3) of the FAM9B gene. This alteration results from a C to T substitution at nucleotide position 152, causing the alanine (A) at amino acid position 51 to be replaced by a valine (V). 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

0.092

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.74

DANN

Benign

0.50

DEOGEN2

Benign

0.0032

.;T;T

FATHMM_MKL

Benign

0.00079

LIST_S2

Benign

0.53

T;T;.

M_CAP

Benign

0.00053

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.81

.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.096

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.98

.;D;D

Vest4

0.084

MutPred

0.14

.;Loss of relative solvent accessibility (P = 0.0981);Loss of relative solvent accessibility (P = 0.0981);

MVP

0.50

MPC

0.051

ClinPred

0.055

GERP RS

-0.47

Varity_R

0.040

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