Variant X-9030267-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_205849.3(FAM9B):c.275T>C(p.Leu92Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000426 in 1,196,205 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000045 ( 0 hom. 11 hem. )

Consequence

FAM9B
NM_205849.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

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:

FAM9B (HGNC:):

FAM9B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM9B	NM_205849.3 linkuse as main transcript	c.275T>C	p.Leu92Pro	missense_variant	5/9	ENST00000327220.10	NP_995321.1	Q8IZU0-1A0A024RBV3
FAM9B	XM_047441882.1 linkuse as main transcript	c.*301T>C		downstream_gene_variant			XP_047297838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM9B	ENST00000327220.10 linkuse as main transcript	c.275T>C	p.Leu92Pro	missense_variant	5/9	1	NM_205849.3	ENSP00000318716.5		Q8IZU0-1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111985

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34189

show subpopulations

Gnomad AFR

AF:

0.0000324

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

161192

Hom.:

AF XY:

0.0000404

AC XY:

AN XY:

49530

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000281

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1084220

Hom.:

Cov.:

AF XY:

0.0000312

AC XY:

AN XY:

352772

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000587

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111985

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34189

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

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 19, 2023

The c.275T>C (p.L92P) alteration is located in exon 4 (coding exon 4) of the FAM9B gene. This alteration results from a T to C substitution at nucleotide position 275, causing the leucine (L) at amino acid position 92 to be replaced by a proline (P). 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

Pathogenic

0.76

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.060

T;T

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.53

T;.

M_CAP

Benign

0.00086

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.11

Sift

Benign

0.11

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.99

D;D

Vest4

0.46

MutPred

0.42

Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);

MVP

0.45

MPC

0.39

ClinPred

0.18

GERP RS

0.23

Varity_R

0.47

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