Genetic Variant FAM47A:p.Arg552Trp (chrX-34130625-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_203408.4(FAM47A):c.1654C>T(p.Arg552Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,207,290 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000013 ( 0 hom. 4 hem. )

Consequence

FAM47A
NM_203408.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.82

Publications

2 publications found

Variant links:

Genes affected

FAM47A (HGNC:29962): (family with sequence similarity 47 member A)

FAM47A links:

ENSG00000233928 (HGNC:):

ENSG00000233928 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046459854).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203408.4. 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
	FAM47A	NM_203408.4	MANE Select	c.1654C>T	p.Arg552Trp	missense	Exon 1 of 1	NP_981953.2	Q5JRC9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM47A	ENST00000346193.5	TSL:6 MANE Select	c.1654C>T	p.Arg552Trp	missense	Exon 1 of 1	ENSP00000345029.3	Q5JRC9
ENSG00000233928	ENST00000653446.1		n.390+54056G>A		intron	N/A
ENSG00000233928	ENST00000656777.1		n.452+54056G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000456

AC:

AN:

109676

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000291

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000221

AC:

AN:

180906

AF XY:

0.0000301

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000736

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000146

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1097567

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

362967

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26376

American (AMR)

AF:

0.0000855

AC:

AN:

35099

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19301

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30201

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54037

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40513

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4124

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841867

Other (OTH)

AF:

0.000174

AC:

AN:

46049

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000456

AC:

AN:

109723

Hom.:

Cov.:

AF XY:

0.0000311

AC XY:

AN XY:

32149

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30145

American (AMR)

AF:

0.000291

AC:

AN:

10314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2609

East Asian (EAS)

AF:

0.000582

AC:

AN:

3435

South Asian (SAS)

AF:

0.00

AC:

AN:

2422

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52513

Other (OTH)

AF:

0.00

AC:

AN:

1476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000214

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000330

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

0.26

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0070

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.65

M_CAP

Benign

0.0012

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

-1.8

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

REVEL

Benign

0.038

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.11

MutPred

0.20

Gain of ubiquitination at K549 (P = 0.0353)

MVP

0.043

MPC

0.74

ClinPred

0.21

GERP RS

-0.92

Varity_R

0.092

gMVP

0.14

Mutation Taster

=100/0

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

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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