chr12-49588534-CC-TA

Variant names:

• chr12-49588534-CC-TA
• NM_032130.3:c.2453_2454delGGinsTA
• FAM186B p.Arg818Leu

Variant summary

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

The NM_032130.3(FAM186B):​c.2453_2454delGGinsTA​(p.Arg818Leu) 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. R818W) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM186B NM_032130.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 0 publications found

Genes affected

FAM186B (HGNC:25296): (family with sequence similarity 186 member B) This gene product is a member of the FAM186 family, however, its exact function is not known. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

PRPF40B (HGNC:25031): (pre-mRNA processing factor 40 homolog B) This gene encodes a WW-domain containing protein similar to yeast splicing factor PRP40. This protein has been shown to interact with Huntingtin and methyl CpG binding protein 2 (MeCP2). Alternative splicing results in different transcript variants. [provided by RefSeq, Aug 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032130.3. 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
	FAM186B	NM_032130.3	MANE Select	c.2453_2454delGGinsTA	p.Arg818Leu	missense	N/A	NP_115506.1	Q8IYM0-1
	FAM186B	NR_027450.2		n.2795_2796delGGinsTA		non_coding_transcript_exon	Exon 6 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM186B	ENST00000257894.2	TSL:1 MANE Select	c.2453_2454delGGinsTA	p.Arg818Leu	missense	N/A	ENSP00000257894.2	Q8IYM0-1
	FAM186B	ENST00000532262.5	TSL:1	c.1292_1293delGGinsTA	p.Arg431Leu	missense	N/A	ENSP00000436995.1	A0A0C4DGG0
	FAM186B	ENST00000548841.5	TSL:5	c.122_123delGGinsTA	p.Arg41Leu	missense	N/A	ENSP00000448989.1	H0YIB0

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27

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: chr12-49982317;