chr4-76268737-A-G

Position:

• chr4-76268737-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136570.3(FAM47E):​c.638A>G​(p.Glu213Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,230 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: FAM47E NM_001136570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.754

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1430099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM47E	NM_001136570.3	c.638A>G	p.Glu213Gly	missense_variant	4/8	ENST00000424749.7
FAM47E-STBD1	NM_001242939.2	c.638A>G	p.Glu213Gly	missense_variant	4/7
FAM47E	NM_001242936.1	c.299A>G	p.Glu100Gly	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM47E	ENST00000424749.7	c.638A>G	p.Glu213Gly	missense_variant	4/8	5	NM_001136570.3	P1
	ENST00000670253.1	n.278-6485T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1399230 Hom.: 0 Cov.: 30 AF XY: 0.00000435 AC XY: 3 AN XY: 690126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2022

The c.638A>G (p.E213G) alteration is located in exon 4 (coding exon 4) of the FAM47E gene. This alteration results from a A to G substitution at nucleotide position 638, causing the glutamic acid (E) at amino acid position 213 to be replaced by a glycine (G). 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	0.091
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.1
DANN	Uncertain	0.99
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.50	T;T;T;T;T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.5	D;D;.;.;D;D;.
REVEL	Benign	0.066
Sift	Uncertain	0.023	D;D;.;.;T;T;.
Sift4G	Benign	0.18	T;T;.;.;T;T;D
Polyphen		0.90	P;P;.;.;P;.;.
Vest4		0.056
MutPred		0.39		.;.;.;.;Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);.;
MVP		0.072
MPC		0.035
ClinPred		0.47	T
GERP RS		1.1
Varity_R		0.066
gMVP		0.092

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: chr4-77189890;