chr4-76263760-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001136570.3(FAM47E):c.477G>T(p.Trp159Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000129 in 1,551,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

FAM47E
NM_001136570.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

Publications

0 publications found

Variant links:

Genes affected

FAM47E (HGNC:34343): (family with sequence similarity 47 member E) Enables enzyme activator activity. Involved in positive regulation of histone methylation and protein localization to chromatin. Located in chromatin; cytoplasm; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM47E links:

FAM47E-STBD1 (HGNC:44667): (FAM47E-STBD1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring FAM47E (family with sequence similarity 47, member E) and STBD1 (starch binding domain 1) genes on chromosome 4. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product but its C-terminal region is distinct due to frameshifts relative to the downstream gene. [provided by RefSeq, Jul 2011]

FAM47E-STBD1 links:

ENSG00000287401 (HGNC:):

ENSG00000287401 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47E	NM_001136570.3 link	c.477G>T	p.Trp159Cys	missense_variant	Exon 3 of 8	ENST00000424749.7	NP_001130042.1	Q6ZV65-3
FAM47E-STBD1	NM_001242939.2 link	c.477G>T	p.Trp159Cys	missense_variant	Exon 3 of 7		NP_001229868.1	Q6ZV65-1
FAM47E	NM_001242936.1 link	c.138G>T	p.Trp46Cys	missense_variant	Exon 3 of 8		NP_001229865.1	Q6ZV65-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47E	ENST00000424749.7 link	c.477G>T	p.Trp159Cys	missense_variant	Exon 3 of 8	5	NM_001136570.3	ENSP00000409423.2		Q6ZV65-3
FAM47E-STBD1	ENST00000515604.5 link	c.477G>T	p.Trp159Cys	missense_variant	Exon 3 of 7	2		ENSP00000422067.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000633

AC:

AN:

157858

AF XY:

0.0000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

7.15e-7

AC:

AN:

1399456

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31586

American (AMR)

AF:

0.0000280

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078884

Other (OTH)

AF:

0.00

AC:

AN:

58074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41362

American (AMR)

AF:

0.0000656

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 07, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.477G>T (p.W159C) alteration is located in exon 3 (coding exon 3) of the FAM47E gene. This alteration results from a G to T substitution at nucleotide position 477, causing the tryptophan (W) at amino acid position 159 to be replaced by a cysteine (C). 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

Pathogenic

0.78

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.077

.;.;T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

D;T;T;T

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.83

D;D;D;D

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.3

.;.;M;.

PhyloP100

4.2

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-11

D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D

Polyphen

1.0

D;.;D;.

Vest4

0.53

MutPred

0.68

.;.;Gain of disorder (P = 0.013);Gain of disorder (P = 0.013);

MVP

0.43

MPC

0.28

ClinPred

0.97

GERP RS

5.0

PromoterAI

-0.0028

Neutral

(source)

Varity_R

0.63

gMVP

0.41

Mutation Taster

=283/17

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over