4-76268698-T-A

Variant names:

• chr4-76268698-T-A
• rs1478634489
• NM_001136570.3:c.599T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136570.3(FAM47E):​c.599T>A​(p.Leu200His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: FAM47E NM_001136570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0150
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106444806).

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.599T>A	p.Leu200His	missense	Exon 4 of 8	NP_001130042.1	Q6ZV65-3
	FAM47E-STBD1	NM_001242939.2		c.599T>A	p.Leu200His	missense	Exon 4 of 7	NP_001229868.1
	FAM47E	NM_001242936.1		c.260T>A	p.Leu87His	missense	Exon 4 of 8	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.599T>A	p.Leu200His	missense	Exon 4 of 8	ENSP00000409423.2	Q6ZV65-3
	FAM47E-STBD1	ENST00000515604.5	TSL:2	c.599T>A	p.Leu200His	missense	Exon 4 of 7	ENSP00000422067.1
	FAM47E	ENST00000853410.1		c.599T>A	p.Leu200His	missense	Exon 4 of 8	ENSP00000523469.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1399196 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 690100

African (AFR) AF: 0.00 AC: 0 AN: 31586

American (AMR) AF: 0.00 AC: 0 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35706

South Asian (SAS) AF: 0.00 AC: 0 AN: 79182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000463 AC: 5 AN: 1078896

Other (OTH) AF: 0.00 AC: 0 AN: 57998

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

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	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.4
DANN	Benign	0.84
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.015
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.12
Sift	Benign	0.12	T
Sift4G	Benign	0.15	T
Polyphen		0.25	B
Vest4		0.24
MutPred		0.39		Loss of helix (P = 0.0093)
MVP		0.19
MPC		0.053
ClinPred		0.60	D
GERP RS		1.1
Varity_R		0.19
gMVP		0.34
Mutation Taster		=85/15	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: rs1478634489; hg19: chr4-77189851;