4-76271631-CCA-TCT

Variant names:

• chr4-76271631-CCA-TCT
• NM_001136570.3:c.733_735delCCAinsTCT
• FAM47E p.Pro245Ser

Variant summary

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

The NM_001136570.3(FAM47E):​c.733_735delCCAinsTCT​(p.Pro245Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. P245A) has been classified 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
• 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.

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.733_735delCCAinsTCT	p.Pro245Ser	missense	N/A	NP_001130042.1	Q6ZV65-3
	FAM47E-STBD1	NM_001242939.2		c.733_735delCCAinsTCT	p.Pro245Ser	missense	N/A	NP_001229868.1
	FAM47E	NM_001242936.1		c.439_441delCCAinsTCT	p.Pro147Ser	missense	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.733_735delCCAinsTCT	p.Pro245Ser	missense	N/A	ENSP00000409423.2	Q6ZV65-3
	FAM47E-STBD1	ENST00000515604.5	TSL:2	c.733_735delCCAinsTCT	p.Pro245Ser	missense	N/A	ENSP00000422067.1
	FAM47E	ENST00000853410.1		c.778_780delCCAinsTCT	p.Pro260Ser	missense	N/A	ENSP00000523469.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.092

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-77192784;