Variant 20-56533429-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001013646.4(FAM209B):c.88A>G(p.Ser30Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

FAM209B
NM_001013646.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.370

Variant links:

Genes affected

FAM209B (HGNC:16101): (family with sequence similarity 209 member B) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM209B links:

FAM209A (HGNC:16100): (family with sequence similarity 209 member A) Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM209A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07979572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM209B	NM_001013646.4 linkuse as main transcript	c.88A>G	p.Ser30Gly	missense_variant	1/2	ENST00000371325.1	NP_001013668.2	Q5JX69
FAM209A	XM_047439964.1 linkuse as main transcript	c.*229A>G		3_prime_UTR_variant	5/5		XP_047295920.1
FAM209A	XM_047439965.1 linkuse as main transcript	c.*382A>G		3_prime_UTR_variant	6/6		XP_047295921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM209B	ENST00000371325.1 linkuse as main transcript	c.88A>G	p.Ser30Gly	missense_variant	1/2	1	NM_001013646.4	ENSP00000360376.1		Q5JX69

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251242

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461418

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Feb 12, 2024

The c.88A>G (p.S30G) alteration is located in exon 1 (coding exon 1) of the FAM209B gene. This alteration results from a A to G substitution at nucleotide position 88, causing the serine (S) at amino acid position 30 to be replaced by a glycine (G). 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

0.083

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.2

DANN

Benign

0.91

DEOGEN2

Benign

0.0060

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.57

M_CAP

Benign

0.0033

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.3

REVEL

Benign

0.036

Sift

Benign

0.10

Sift4G

Benign

0.19

Polyphen

0.091

Vest4

0.15

MVP

0.048

MPC

0.52

ClinPred

0.031

GERP RS

1.6

Varity_R

0.066

gMVP

0.046

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