dbSNP rs866894892: FAM47E:p.Glu18Lys (chr4-76251798-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136570.3(FAM47E):c.52G>A(p.Glu18Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E18Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM47E
NM_001136570.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00400

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039340317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47E	NM_001136570.3 link	c.52G>A	p.Glu18Lys	missense_variant	Exon 1 of 8	ENST00000424749.7	NP_001130042.1	Q6ZV65-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47E	ENST00000424749.7 link	c.52G>A	p.Glu18Lys	missense_variant	Exon 1 of 8	5	NM_001136570.3	ENSP00000409423.2		Q6ZV65-3
FAM47E-STBD1	ENST00000515604.5 link	c.52G>A	p.Glu18Lys	missense_variant	Exon 1 of 7	2		ENSP00000422067.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1338300

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

658956

African (AFR)

AF:

0.00

AC:

AN:

27072

American (AMR)

AF:

0.00

AC:

AN:

30688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23450

East Asian (EAS)

AF:

0.00

AC:

AN:

30720

South Asian (SAS)

AF:

0.00

AC:

AN:

74478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4518

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1058752

Other (OTH)

AF:

0.00

AC:

AN:

55712

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000358

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.5

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0049

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.

PhyloP100

0.0040

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.61

N;N

REVEL

Benign

0.054

Sift

Benign

0.38

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0050

B;.

Vest4

0.088

MutPred

0.26

Gain of methylation at E18 (P = 0.0103);Gain of methylation at E18 (P = 0.0103);

MVP

0.014

MPC

0.032

ClinPred

0.027

GERP RS

0.29

PromoterAI

0.11

Neutral

(source)

Varity_R

0.032

gMVP

0.13

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over