4-76251798-G-T

Variant names:

• chr4-76251798-G-T
• rs866894892
• NM_001136570.3:c.52G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001136570.3(FAM47E):​c.52G>T​(p.Glu18*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,338,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FAM47E NM_001136570.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 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.52G>T	p.Glu18*	stop_gained	Exon 1 of 8	ENST00000424749.7	NP_001130042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47E	ENST00000424749.7	c.52G>T	p.Glu18*	stop_gained	Exon 1 of 8	5	NM_001136570.3	ENSP00000409423.2
FAM47E-STBD1	ENST00000515604.5	c.52G>T	p.Glu18*	stop_gained	Exon 1 of 7	2		ENSP00000422067.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1338300 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 658956

African (AFR) AF: 0.00 AC: 0 AN: 27072

American (AMR) AF: 0.00 AC: 0 AN: 30688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23450

East Asian (EAS) AF: 0.00 AC: 0 AN: 30720

South Asian (SAS) AF: 0.00 AC: 0 AN: 74478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4518

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1058752

Other (OTH) AF: 0.00 AC: 0 AN: 55712

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	30
DANN	Benign	0.96
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.24	N
PhyloP100		0.0040
Vest4		0.037
GERP RS		0.29
PromoterAI		0.0056	Neutral
Mutation Taster		=84/116	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs866894892; hg19: chr4-77172951;