Genetic Variant NM_001012971.4:c.505A>G (chr20-56526059-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001012971.4(FAM209A):c.505A>G(p.Ser169Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,600,590 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

FAM209A
NM_001012971.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.684

Publications

1 publications found

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]

FAM209A links:

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]

GCNT7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05148062).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012971.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM209A	NM_001012971.4	MANE Select	c.505A>G	p.Ser169Gly	missense	Exon 2 of 2	NP_001012989.2	Q5JX71
	GCNT7	NR_160308.1		n.-134T>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM209A	ENST00000371328.5	TSL:1 MANE Select	c.505A>G	p.Ser169Gly	missense	Exon 2 of 2	ENSP00000360379.4	Q5JX71
FAM209A	ENST00000481560.1	TSL:5	n.650A>G		non_coding_transcript_exon	Exon 4 of 4
GCNT7	ENST00000243913.8	TSL:2	c.-1206T>C		upstream_gene	N/A	ENSP00000243913.4	Q6ZNI0

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152212

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000412

AC:

AN:

242632

AF XY:

0.0000687

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000811

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000217

AC:

315

AN:

1448378

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

141

AN XY:

718968

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32910

American (AMR)

AF:

0.00

AC:

AN:

42908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25520

East Asian (EAS)

AF:

0.00

AC:

AN:

39542

South Asian (SAS)

AF:

0.00

AC:

AN:

83998

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.000277

AC:

306

AN:

1105052

Other (OTH)

AF:

0.000134

AC:

AN:

59766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000286

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.011

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00053

LIST_S2

Benign

0.32

M_CAP

Benign

0.0023

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PhyloP100

0.68

PROVEAN

Benign

-0.96

REVEL

Benign

0.027

Sift

Benign

0.034

Sift4G

Benign

0.066

Polyphen

0.19

Vest4

0.053

MutPred

0.19

Loss of phosphorylation at S169 (P = 0.0349)

MVP

0.014

MPC

0.20

ClinPred

0.025

GERP RS

1.9

PromoterAI

0.0030

Neutral

(source)

Varity_R

0.065

gMVP

0.021

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over