4-76256260-G-C

Variant names:

• chr4-76256260-G-C
• NM_001136570.3:c.157G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136570.3(FAM47E):​c.157G>C​(p.Asp53His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM47E NM_001136570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82

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-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]

ENSG00000287401 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47E	NM_001136570.3	c.157G>C	p.Asp53His	missense_variant	Exon 2 of 8	ENST00000424749.7	NP_001130042.1
FAM47E-STBD1	NM_001242939.2	c.157G>C	p.Asp53His	missense_variant	Exon 2 of 7		NP_001229868.1
FAM47E	NM_001242936.1	c.82-7444G>C		intron_variant	Intron 2 of 7		NP_001229865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47E	ENST00000424749.7	c.157G>C	p.Asp53His	missense_variant	Exon 2 of 8	5	NM_001136570.3	ENSP00000409423.2
FAM47E-STBD1	ENST00000515604.5	c.157G>C	p.Asp53His	missense_variant	Exon 2 of 7	2		ENSP00000422067.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.157G>C (p.D53H) alteration is located in exon 2 (coding exon 2) of the FAM47E gene. This alteration results from a G to C substitution at nucleotide position 157, causing the aspartic acid (D) at amino acid position 53 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	0.21
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;.
Vest4		0.50
MutPred		0.50		Loss of glycosylation at K50 (P = 0.0491);Loss of glycosylation at K50 (P = 0.0491);
MVP		0.29
MPC		0.25
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.55
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-77177413;