6-3850064-G-T

Variant names:

• chr6-3850064-G-T
• rs755628628
• NM_012135.3:c.253G>T

Variant summary

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

The NM_012135.3(FAM50B):​c.253G>T​(p.Glu85*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM50B NM_012135.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.76
• 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.253G>T	p.Glu85*	stop_gained	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.253G>T	p.Glu85*	stop_gained	Exon 2 of 2	ENSP00000496837.1	Q9Y247
	FAM50B	ENST00000380274.2	TSL:6	c.253G>T	p.Glu85*	stop_gained	Exon 1 of 1	ENSP00000369627.1	Q9Y247
	FAM50B	ENST00000895441.1		c.253G>T	p.Glu85*	stop_gained	Exon 2 of 2	ENSP00000565500.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241486 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000924

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458960 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725688

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111040

Other (OTH) AF: 0.00 AC: 0 AN: 60198

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.89	D
PhyloP100		8.8
Vest4		0.083
GERP RS		3.5
Mutation Taster		=38/162	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: rs755628628; hg19: chr6-3850298;