chr20-56524828-C-T

Position:

chr20-56524828-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001012971.4(FAM209A):c.20C>T(p.Ser7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

FAM209A
NM_001012971.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00900

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017377138).

BP6

Variant 20-56524828-C-T is Benign according to our data. Variant chr20-56524828-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3092243.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM209A	NM_001012971.4 linkuse as main transcript	c.20C>T	p.Ser7Phe	missense_variant	1/2	ENST00000371328.5
GCNT7	NR_160308.1 linkuse as main transcript	n.143+955G>A		intron_variant, non_coding_transcript_variant
FAM209A	XM_047439964.1 linkuse as main transcript	c.20C>T	p.Ser7Phe	missense_variant	1/5
FAM209A	XM_047439965.1 linkuse as main transcript	c.20C>T	p.Ser7Phe	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAM209A	ENST00000371328.5 linkuse as main transcript	c.20C>T	p.Ser7Phe	missense_variant	1/2	1	NM_001012971.4	P1
GCNT7	ENST00000243913.8 linkuse as main transcript	c.-930+955G>A		intron_variant		2		P1
FAM209A	ENST00000481560.1 linkuse as main transcript	n.227-62C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000955

AC:

AN:

251420

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.000324

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000153

AC:

224

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.000173

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000151

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000183

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.7

DANN

Benign

0.69

DEOGEN2

Benign

0.0027

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.33

M_CAP

Benign

0.0021

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.55

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

3.4

REVEL

Benign

0.014

Sift

Benign

1.0

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.080

MVP

0.040

MPC

0.23

ClinPred

0.043

GERP RS

-1.2

Varity_R

0.035

gMVP

0.066

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