NM_001136570.3:c.599T>A

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.599T>A(p.Leu200His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,196 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: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

FAM47E
NM_001136570.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0150

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=0.106444806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47E	NM_001136570.3 link	c.599T>A	p.Leu200His	missense_variant	Exon 4 of 8	ENST00000424749.7	NP_001130042.1	Q6ZV65-3
FAM47E-STBD1	NM_001242939.2 link	c.599T>A	p.Leu200His	missense_variant	Exon 4 of 7		NP_001229868.1	Q6ZV65-1
FAM47E	NM_001242936.1 link	c.260T>A	p.Leu87His	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.599T>A	p.Leu200His	missense_variant	Exon 4 of 8	5	NM_001136570.3	ENSP00000409423.2		Q6ZV65-3
FAM47E-STBD1	ENST00000515604.5 link	c.599T>A	p.Leu200His	missense_variant	Exon 4 of 7	2		ENSP00000422067.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1399196

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31586

American (AMR)

AF:

0.00

AC:

AN:

35682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35706

South Asian (SAS)

AF:

0.00

AC:

AN:

79182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00000463

AC:

AN:

1078896

Other (OTH)

AF:

0.00

AC:

AN:

57998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.599T>A (p.L200H) alteration is located in exon 4 (coding exon 4) of the FAM47E gene. This alteration results from a T to A substitution at nucleotide position 599, causing the leucine (L) at amino acid position 200 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

9.4

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.051

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

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.58

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

M_CAP

Benign

0.035

MetaRNN

Benign

0.11

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

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

.;.;.;.;M;.;.

PhyloP100

0.015

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-4.3

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

REVEL

Benign

0.12

Sift

Benign

0.12

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

Sift4G

Benign

0.15

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

Polyphen

0.25

B;P;.;.;B;.;.

Vest4

0.24

MutPred

0.39

.;.;.;.;Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);.;

MVP

0.19

MPC

0.053

ClinPred

0.60

GERP RS

1.1

Varity_R

0.19

gMVP

0.34

Mutation Taster

=85/15

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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NM_001136570.3:c.599T>A

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