NM_012135.3:c.491G>C

Variant names:

• chr6-3850302-G-C
• rs1308750625
• NM_012135.3:c.491G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012135.3(FAM50B):​c.491G>C​(p.Arg164Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM50B NM_012135.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26
• Publications: 0 publications found

Genes affected

FAM50B (HGNC:18789): (family with sequence similarity 50 member B) This gene contains an intronless ORF that arose from ancestral retroposition. The encoded protein is related to a plant protein that plays a role in the circadian clock. This gene is adjacent to a differentially methylated region (DMR) and is imprinted and paternally expressed in many tissues. [provided by RefSeq, Nov 2015]

ENSG00000301665 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012135.3. 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
	FAM50B	NM_012135.3	MANE Select	c.491G>C	p.Arg164Pro	missense	Exon 2 of 2	NP_036267.1	Q9Y247

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM50B	ENST00000648326.1	MANE Select	c.491G>C	p.Arg164Pro	missense	Exon 2 of 2	ENSP00000496837.1	Q9Y247
	FAM50B	ENST00000380274.2	TSL:6	c.491G>C	p.Arg164Pro	missense	Exon 1 of 1	ENSP00000369627.1	Q9Y247
	FAM50B	ENST00000895441.1		c.491G>C	p.Arg164Pro	missense	Exon 2 of 2	ENSP00000565500.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460970 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726798

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111744

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.3
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.26
Sift	Benign	0.042	D
Sift4G	Benign	0.17	T
Polyphen		0.98	D
Vest4		0.40
MutPred		0.52		Loss of helix (P = 0.0304)
MVP		0.62
MPC		2.2
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.87
gMVP		0.78
Mutation Taster		=28/72	disease causing

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

Other links and lift over

dbSNP: rs1308750625; hg19: chr6-3850536;