NM_001136570.3:c.52G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136570.3(FAM47E):​c.52G>C​(p.Glu18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,338,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: FAM47E NM_001136570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044838756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136570.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47E	NM_001136570.3	MANE Select	c.52G>C	p.Glu18Gln	missense	Exon 1 of 8	NP_001130042.1	Q6ZV65-3
	FAM47E-STBD1	NM_001242939.2		c.52G>C	p.Glu18Gln	missense	Exon 1 of 7	NP_001229868.1
	FAM47E	NM_001242936.1		c.82-11906G>C		intron	N/A	NP_001229865.1	Q6ZV65-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47E	ENST00000424749.7	TSL:5 MANE Select	c.52G>C	p.Glu18Gln	missense	Exon 1 of 8	ENSP00000409423.2	Q6ZV65-3
	FAM47E-STBD1	ENST00000515604.5	TSL:2	c.52G>C	p.Glu18Gln	missense	Exon 1 of 7	ENSP00000422067.1
	FAM47E	ENST00000853410.1		c.52G>C	p.Glu18Gln	missense	Exon 1 of 8	ENSP00000523469.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.47e-7 AC: 1 AN: 1338300 Hom.: 0 Cov.: 31 AF XY: 0.00000152 AC XY: 1 AN XY: 658956

African (AFR) AF: 0.0000369 AC: 1 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: 0.00 AC: 0 AN: 1058752

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.8
DANN	Benign	0.60
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.0040
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.051
Sift	Benign	0.35	T
Sift4G	Benign	0.47	T
Polyphen		0.43	B
Vest4		0.090
MutPred		0.15		Gain of MoRF binding (P = 0.0522)
MVP		0.030
MPC		0.036
ClinPred		0.037	T
GERP RS		0.29
PromoterAI		0.052	Neutral
Varity_R		0.048
gMVP		0.094
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs866894892; hg19: chr4-77172951;