rs376467863

Variant names:

• chr6-3850159-G-C
• rs376467863
• NM_012135.3:c.348G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012135.3(FAM50B):​c.348G>C​(p.Lys116Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,612,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: FAM50B NM_012135.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.084288806).

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.348G>C	p.Lys116Asn	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.348G>C	p.Lys116Asn	missense	Exon 2 of 2	ENSP00000496837.1	Q9Y247
	FAM50B	ENST00000380274.2	TSL:6	c.348G>C	p.Lys116Asn	missense	Exon 1 of 1	ENSP00000369627.1	Q9Y247
	FAM50B	ENST00000895441.1		c.348G>C	p.Lys116Asn	missense	Exon 2 of 2	ENSP00000565500.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000771 AC: 19 AN: 246542 AF XY: 0.000112

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: 0.000163

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000205 AC: 299 AN: 1460716 Hom.: 1 Cov.: 31 AF XY: 0.000204 AC XY: 148 AN XY: 726714

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52678

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

European-Non Finnish (NFE) AF: 0.000255 AC: 283 AN: 1111778

Other (OTH) AF: 0.000249 AC: 15 AN: 60338

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74376

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68050

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000680

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000907 AC: 11

EpiCase AF: 0.000109

EpiControl AF: 0.000237

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	Uncertain	0.52
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.084	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.090
Sift	Benign	0.036	D
Sift4G	Uncertain	0.038	D
Polyphen		0.026	B
Vest4		0.10
MutPred		0.42		Loss of methylation at K116 (P = 0.0046)
MVP		0.25
MPC		1.4
ClinPred		0.051	T
GERP RS		3.4
Varity_R		0.22
gMVP		0.42
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs376467863; hg19: chr6-3850393;