Genetic Variant FAM47A:p.Phe679Leu (chrX-34130242-G-C) – 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.2037C>G(p.Phe679Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 1,209,129 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000038 ( 0 hom. 17 hem. )

Consequence

FAM47A
NM_203408.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.01

Publications

0 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=0.024711281).

BS2

High Hemizygotes in GnomAdExome4 at 17 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.2037C>G	p.Phe679Leu	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.2037C>G	p.Phe679Leu	missense	Exon 1 of 1	ENSP00000345029.3	Q5JRC9
ENSG00000233928	ENST00000653446.1		n.390+53673G>C		intron	N/A
ENSG00000233928	ENST00000656777.1		n.452+53673G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111970

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000165

AC:

AN:

181421

AF XY:

0.0000302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1097159

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

362551

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26372

American (AMR)

AF:

0.00

AC:

AN:

35091

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19306

East Asian (EAS)

AF:

0.00

AC:

AN:

30194

South Asian (SAS)

AF:

0.00

AC:

AN:

53880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.0000380

AC:

AN:

841624

Other (OTH)

AF:

0.000217

AC:

AN:

46048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.0000179

AC:

AN:

111970

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30765

American (AMR)

AF:

0.00

AC:

AN:

10542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3546

South Asian (SAS)

AF:

0.00

AC:

AN:

2688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53219

Other (OTH)

AF:

0.00

AC:

AN:

1504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

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

Uncertain

0.54

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.027

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.0034

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.19

M_CAP

Benign

0.00069

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.4

PhyloP100

-1.0

PrimateAI

Benign

0.47

PROVEAN

Benign

0.60

REVEL

Benign

0.011

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0040

Vest4

0.030

MutPred

0.20

Gain of catalytic residue at F679 (P = 0.0227)

MVP

0.043

MPC

0.23

ClinPred

0.034

GERP RS

-0.58

Varity_R

0.035

gMVP

0.025

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