chr4-76263734-C-G

Variant names:

• chr4-76263734-C-G
• rs1399946482
• NM_001136570.3:c.451C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136570.3(FAM47E):​c.451C>G​(p.Pro151Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P151S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM47E NM_001136570.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40197086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47E	NM_001136570.3	c.451C>G	p.Pro151Ala	missense_variant	Exon 3 of 8	ENST00000424749.7	NP_001130042.1
FAM47E-STBD1	NM_001242939.2	c.451C>G	p.Pro151Ala	missense_variant	Exon 3 of 7		NP_001229868.1
FAM47E	NM_001242936.1	c.112C>G	p.Pro38Ala	missense_variant	Exon 3 of 8		NP_001229865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47E	ENST00000424749.7	c.451C>G	p.Pro151Ala	missense_variant	Exon 3 of 8	5	NM_001136570.3	ENSP00000409423.2
FAM47E-STBD1	ENST00000515604.5	c.451C>G	p.Pro151Ala	missense_variant	Exon 3 of 7	2		ENSP00000422067.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.78
DEOGEN2	Benign	0.19	.;.;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.76	T;T;D;D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.9	.;.;M;.
PhyloP100		2.0
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-6.7	D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.016	D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.53
MutPred		0.36		.;.;Loss of glycosylation at K154 (P = 0.08);Loss of glycosylation at K154 (P = 0.08);
MVP		0.58
MPC		0.23
ClinPred		0.98	D
GERP RS		5.0
PromoterAI		0.011	Neutral
Varity_R		0.27
gMVP		0.33
Mutation Taster		=74/26	polymorphism

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: rs1399946482; hg19: chr4-77184887;