6-3850064-G-A

Position:

• chr6-3850064-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012135.3(FAM50B):​c.253G>A​(p.Glu85Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM50B NM_012135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.76

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37950674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM50B	NM_012135.3	c.253G>A	p.Glu85Lys	missense_variant	2/2	ENST00000648326.1
FAM50B	XM_017010729.2	c.253G>A	p.Glu85Lys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM50B	ENST00000648326.1	c.253G>A	p.Glu85Lys	missense_variant	2/2		NM_012135.3	P1
	ENST00000454396.2	n.80-5406G>A		intron_variant, non_coding_transcript_variant		5
	ENST00000648025.1	n.76+18053G>A		intron_variant, non_coding_transcript_variant
FAM50B	ENST00000380274.2	c.253G>A	p.Glu85Lys	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458960 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725688

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	0.0052	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T;T;T
Eigen	Benign	-0.044
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.66	T
Polyphen		0.72	P;P;P
Vest4		0.35, 0.41
MutPred		0.34		Loss of ubiquitination at K90 (P = 0.0219);Loss of ubiquitination at K90 (P = 0.0219);Loss of ubiquitination at K90 (P = 0.0219);
MVP		0.56
MPC		1.0
ClinPred		0.95	D
GERP RS		3.5
Varity_R		0.25
gMVP		0.73

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: rs755628628; hg19: chr6-3850298;