NM_032130.3:c.2326C>G

Variant names:

• chr12-49598793-G-C
• rs765632091
• NM_032130.3:c.2326C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032130.3(FAM186B):​c.2326C>G​(p.Arg776Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM186B NM_032130.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06433195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM186B	NM_032130.3	c.2326C>G	p.Arg776Gly	missense_variant	Exon 5 of 7	ENST00000257894.2	NP_115506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM186B	ENST00000257894.2	c.2326C>G	p.Arg776Gly	missense_variant	Exon 5 of 7	1	NM_032130.3	ENSP00000257894.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.087	T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.054
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.019	.;B
Vest4		0.53
MutPred		0.24		.;Loss of helix (P = 0.0304);
MVP		0.040
MPC		0.42
ClinPred		0.12	T
GERP RS		-1.8
Varity_R		0.064
gMVP		0.082

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: rs765632091; hg19: chr12-49992576;