chr4-76271631-C-G

Position:

• chr4-76271631-C-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.733C>G​(p.Pro245Ala) 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. 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)
• Consequence: FAM47E NM_001136570.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=0.10145736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM47E	NM_001136570.3	c.733C>G	p.Pro245Ala	missense_variant	5/8	ENST00000424749.7
FAM47E-STBD1	NM_001242939.2	c.733C>G	p.Pro245Ala	missense_variant	5/7
FAM47E	NM_001242936.1	c.439C>G	p.Pro147Ala	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM47E	ENST00000424749.7	c.733C>G	p.Pro245Ala	missense_variant	5/8	5	NM_001136570.3	P1
	ENST00000670253.1	n.278-9379G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.90
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.52	T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.5	D;.;D;D;.
REVEL	Benign	0.063
Sift	Benign	0.26	T;.;T;T;.
Sift4G	Benign	0.27	T;.;T;T;D
Polyphen		0.89	P;.;P;.;.
Vest4		0.20
MutPred		0.42		.;.;Gain of glycosylation at Y241 (P = 0.027);Gain of glycosylation at Y241 (P = 0.027);.;
MVP		0.088
MPC		0.11
ClinPred		0.31	T
GERP RS		-0.033
Varity_R		0.057
gMVP		0.12

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

LitVar

Other links and lift over

dbSNP: rs1159083272; hg19: chr4-77192784;