6-3850319-C-G

Variant names:

• chr6-3850319-C-G
• NM_012135.3:c.508C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_012135.3(FAM50B):​c.508C>G​(p.Arg170Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,020 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R170C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM50B NM_012135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544

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]

ENSG00000238158 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM50B	NM_012135.3	c.508C>G	p.Arg170Gly	missense_variant	Exon 2 of 2	ENST00000648326.1	NP_036267.1
FAM50B	XM_017010729.2	c.508C>G	p.Arg170Gly	missense_variant	Exon 2 of 2		XP_016866218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM50B	ENST00000648326.1	c.508C>G	p.Arg170Gly	missense_variant	Exon 2 of 2		NM_012135.3	ENSP00000496837.1
FAM50B	ENST00000380274.2	c.508C>G	p.Arg170Gly	missense_variant	Exon 1 of 1	6		ENSP00000369627.1
ENSG00000238158	ENST00000454396.2	n.80-5151C>G		intron_variant	Intron 1 of 1	5
ENSG00000233068	ENST00000648025.1	n.76+18308C>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461020 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726826

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: 0.00

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.94	.;.;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.1	M;M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.6	.;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	.;D;D
Sift4G	Uncertain	0.0080	.;D;D
Polyphen		0.99	D;D;D
Vest4		0.33, 0.34
MutPred		0.65		Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);
MVP		0.54
MPC		2.2
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.61
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-3850553;