chr6-3850410-C-A

Variant names:

• chr6-3850410-C-A
• rs144921822
• NM_012135.3:c.599C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012135.3(FAM50B):​c.599C>A​(p.Thr200Lys) 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 benign outcome for this variant. 14/20 in silico tools predict a benign 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. T200M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM50B NM_012135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12469447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM50B	NM_012135.3	c.599C>A	p.Thr200Lys	missense_variant	Exon 2 of 2	ENST00000648326.1	NP_036267.1
FAM50B	XM_017010729.2	c.599C>A	p.Thr200Lys	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.599C>A	p.Thr200Lys	missense_variant	Exon 2 of 2		NM_012135.3	ENSP00000496837.1
FAM50B	ENST00000380274.2	c.599C>A	p.Thr200Lys	missense_variant	Exon 1 of 1	6		ENSP00000369627.1
ENSG00000238158	ENST00000454396.2	n.80-5060C>A		intron_variant	Intron 1 of 1	5
ENSG00000233068	ENST00000648025.1	n.76+18399C>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	0.0016	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.037	T;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.46	N
LIST_S2	Pathogenic	0.97	.;.;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.3	.;N;N
REVEL	Benign	0.13
Sift	Benign	0.22	.;T;T
Sift4G	Benign	0.57	.;T;T
Polyphen		0.089	B;B;B
Vest4		0.27, 0.30
MutPred		0.34		Loss of phosphorylation at T200 (P = 0.0105);Loss of phosphorylation at T200 (P = 0.0105);Loss of phosphorylation at T200 (P = 0.0105);
MVP		0.27
MPC		1.1
ClinPred		0.35	T
GERP RS		2.5
Varity_R		0.16
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs144921822; hg19: chr6-3850644;