chr20-56524906-A-G

Variant summary

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

The NM_001012971.4(FAM209A):ā€‹c.98A>Gā€‹(p.Gln33Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000017 ( 0 hom. )

Consequence

FAM209A
NM_001012971.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.406
Variant links:
Genes affected
FAM209A (HGNC:16100): (family with sequence similarity 209 member A) Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
GCNT7 (HGNC:16099): (glucosaminyl (N-acetyl) transferase family member 7) Predicted to enable acetylglucosaminyltransferase activity. Predicted to be involved in protein glycosylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08569223).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAM209ANM_001012971.4 linkuse as main transcriptc.98A>G p.Gln33Arg missense_variant 1/2 ENST00000371328.5
GCNT7NR_160308.1 linkuse as main transcriptn.143+877T>C intron_variant, non_coding_transcript_variant
FAM209AXM_047439964.1 linkuse as main transcriptc.98A>G p.Gln33Arg missense_variant 1/5
FAM209AXM_047439965.1 linkuse as main transcriptc.98A>G p.Gln33Arg missense_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAM209AENST00000371328.5 linkuse as main transcriptc.98A>G p.Gln33Arg missense_variant 1/21 NM_001012971.4 P1
GCNT7ENST00000243913.8 linkuse as main transcriptc.-930+877T>C intron_variant 2 P1
FAM209AENST00000481560.1 linkuse as main transcriptn.243A>G non_coding_transcript_exon_variant 3/45

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251458
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000463
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461606
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727086
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152192
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000494
AC:
6

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 submitterclinical testingAmbry GeneticsFeb 27, 2023The c.98A>G (p.Q33R) alteration is located in exon 1 (coding exon 1) of the FAM209A gene. This alteration results from a A to G substitution at nucleotide position 98, causing the glutamine (Q) at amino acid position 33 to be replaced by an arginine (R). 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
0.089
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
9.2
DANN
Benign
0.96
DEOGEN2
Benign
0.037
T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.46
T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.086
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
N;N
PROVEAN
Benign
-2.4
N
REVEL
Benign
0.044
Sift
Benign
0.22
T
Sift4G
Benign
0.41
T
Polyphen
0.96
D
Vest4
0.17
MutPred
0.19
Loss of ubiquitination at K28 (P = 0.0213);
MVP
0.067
MPC
0.81
ClinPred
0.13
T
GERP RS
-3.9
Varity_R
0.074
gMVP
0.080

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.

Other links and lift over

dbSNP: rs768502335; hg19: chr20-55099962; API