4-76256254-G-A

Position:

• chr4-76256254-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001136570.3(FAM47E):​c.151G>A​(p.Gly51Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM47E NM_001136570.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.60

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:):

ACMG classification

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=0.14619753).
• BP6: Variant 4-76256254-G-A is Benign according to our data. Variant chr4-76256254-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2476170.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM47E	NM_001136570.3	c.151G>A	p.Gly51Arg	missense_variant	2/8	ENST00000424749.7
FAM47E-STBD1	NM_001242939.2	c.151G>A	p.Gly51Arg	missense_variant	2/7
FAM47E	NM_001242936.1	c.82-7450G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM47E	ENST00000424749.7	c.151G>A	p.Gly51Arg	missense_variant	2/8	5	NM_001136570.3	P1
	ENST00000670253.1	n.554+681C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.87
DEOGEN2	Benign	0.091	T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Benign	0.11
Sift	Benign	0.073	T;T
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.24	B;.
Vest4		0.21
MutPred		0.41		Gain of MoRF binding (P = 0.0389);Gain of MoRF binding (P = 0.0389);
MVP		0.076
MPC		0.049
ClinPred		0.33	T
GERP RS		3.3
Varity_R		0.24
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr4-77177407;