Variant chr4-76278070-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136570.3(FAM47E):c.872A>G(p.Asn291Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,493,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

FAM47E
NM_001136570.3 missense, splice_region

Scores

Splicing: ADA: 0.1361

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

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:):

FAM47E-STBD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05629927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM47E	NM_001136570.3 linkuse as main transcript	c.872A>G	p.Asn291Ser	missense_variant, splice_region_variant	6/8	ENST00000424749.7
FAM47E-STBD1	NM_001242939.2 linkuse as main transcript	c.872A>G	p.Asn291Ser	missense_variant, splice_region_variant	6/7
FAM47E	NM_001242936.1 linkuse as main transcript	c.578A>G	p.Asn193Ser	missense_variant, splice_region_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM47E	ENST00000424749.7 linkuse as main transcript	c.872A>G	p.Asn291Ser	missense_variant, splice_region_variant	6/8	5	NM_001136570.3	P1	Q6ZV65-3
	ENST00000670253.1 linkuse as main transcript	n.278-15818T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000478

GnomAD3 exomes

AF:

0.0000183

AC:

AN:

109512

Hom.:

AF XY:

0.0000343

AC XY:

AN XY:

58264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000969

AC:

AN:

1341370

Hom.:

Cov.:

AF XY:

0.0000121

AC XY:

AN XY:

660096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000294

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000661

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.00000756

ExAC

AF:

0.0000246

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.69

T;T;T;T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.040

T;T;T;T;T

MetaSVM

Benign

-0.44

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.8

D;.;.;D;D

REVEL

Benign

0.27

Sift

Benign

0.046

D;.;.;T;T

Sift4G

Uncertain

0.027

D;.;.;T;D

Polyphen

0.97

D;.;.;P;.

Vest4

0.13

MVP

0.42

MPC

0.070

ClinPred

0.76

GERP RS

5.0

Varity_R

0.14

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.14

dbscSNV1_RF

Benign

0.21

SpliceAI score (max)

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over