chr4-76268737-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136570.3(FAM47E):c.638A>G(p.Glu213Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

FAM47E
NM_001136570.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.754

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1430099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47E	NM_001136570.3 link	c.638A>G	p.Glu213Gly	missense_variant	Exon 4 of 8	ENST00000424749.7	NP_001130042.1	Q6ZV65-3
FAM47E-STBD1	NM_001242939.2 link	c.638A>G	p.Glu213Gly	missense_variant	Exon 4 of 7		NP_001229868.1	Q6ZV65-1
FAM47E	NM_001242936.1 link	c.299A>G	p.Glu100Gly	missense_variant	Exon 4 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.638A>G	p.Glu213Gly	missense_variant	Exon 4 of 8	5	NM_001136570.3	ENSP00000409423.2		Q6ZV65-3
FAM47E-STBD1	ENST00000515604.5 link	c.638A>G	p.Glu213Gly	missense_variant	Exon 4 of 7	2		ENSP00000422067.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399230

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31588

American (AMR)

AF:

0.00

AC:

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25174

East Asian (EAS)

AF:

0.00

AC:

AN:

35700

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49270

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078892

Other (OTH)

AF:

0.00

AC:

AN:

57998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 23, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.638A>G (p.E213G) alteration is located in exon 4 (coding exon 4) of the FAM47E gene. This alteration results from a A to G substitution at nucleotide position 638, causing the glutamic acid (E) at amino acid position 213 to be replaced by a glycine (G). 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

Benign

0.091

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.1

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

.;.;.;.;T;.;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.50

T;T;T;T;T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.14

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

.;.;.;.;L;.;.

PhyloP100

0.75

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.5

D;D;.;.;D;D;.

REVEL

Benign

0.066

Sift

Uncertain

0.023

D;D;.;.;T;T;.

Sift4G

Benign

0.18

T;T;.;.;T;T;D

Polyphen

0.90

P;P;.;.;P;.;.

Vest4

0.056

MutPred

0.39

.;.;.;.;Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);.;

MVP

0.072

MPC

0.035

ClinPred

0.47

GERP RS

1.1

Varity_R

0.066

gMVP

0.092

Mutation Taster

=92/8

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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chr4-76268737-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over