rs750428859

Variant names:

• chr6-3850319-C-A
• rs750428859
• NM_012135.3:c.508C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-3850319-C-A
• chr6-3850319-C-G
• chr6-3850319-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012135.3(FAM50B):​c.508C>A​(p.Arg170Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM50B	NM_012135.3	c.508C>A	p.Arg170Ser	missense_variant	Exon 2 of 2	ENST00000648326.1	NP_036267.1
FAM50B	XM_017010729.2	c.508C>A	p.Arg170Ser	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>A	p.Arg170Ser	missense_variant	Exon 2 of 2		NM_012135.3	ENSP00000496837.1
FAM50B	ENST00000380274.2	c.508C>A	p.Arg170Ser	missense_variant	Exon 1 of 1	6		ENSP00000369627.1
ENSG00000238158	ENST00000454396.2	n.80-5151C>A		intron_variant	Intron 1 of 1	5
ENSG00000233068	ENST00000648025.1	n.76+18308C>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.94	.;.;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.1	M;M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.6	.;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	.;D;D
Sift4G	Uncertain	0.011	.;D;D
Polyphen		0.99	D;D;D
Vest4		0.29, 0.32
MutPred		0.62		Gain of phosphorylation at R170 (P = 0.0092);Gain of phosphorylation at R170 (P = 0.0092);Gain of phosphorylation at R170 (P = 0.0092);
MVP		0.59
MPC		2.1
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.69
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

LitVar

Other links and lift over

dbSNP: rs750428859; hg19: chr6-3850553; COSMIC: COSV66654664;