NM_012135.3:c.599C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_012135.3(FAM50B):​c.599C>T​(p.Thr200Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 1,613,332 control chromosomes in the GnomAD database, including 3 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 0.00060 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (3 hom.)
• Consequence: FAM50B NM_012135.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35
• Publications: 5 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012669772).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.599C>T	p.Thr200Met	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.599C>T	p.Thr200Met	missense	Exon 2 of 2	ENSP00000496837.1	Q9Y247
	FAM50B	ENST00000380274.2	TSL:6	c.599C>T	p.Thr200Met	missense	Exon 1 of 1	ENSP00000369627.1	Q9Y247
	FAM50B	ENST00000895441.1		c.599C>T	p.Thr200Met	missense	Exon 2 of 2	ENSP00000565500.1

Frequencies

GnomAD3 genomes AF: 0.000598 AC: 91 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000641 AC: 160 AN: 249732 AF XY: 0.000606

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00509

Gnomad EAS exome AF: 0.000274

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000399

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.000482 AC: 704 AN: 1461022 Hom.: 3 Cov.: 31 AF XY: 0.000495 AC XY: 360 AN XY: 726862

African (AFR) AF: 0.000269 AC: 9 AN: 33474

American (AMR) AF: 0.00119 AC: 53 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00609 AC: 159 AN: 26106

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39694

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52754

Middle Eastern (MID) AF: 0.00624 AC: 36 AN: 5768

European-Non Finnish (NFE) AF: 0.000305 AC: 339 AN: 1111902

Other (OTH) AF: 0.00101 AC: 61 AN: 60374

GnomAD4 genome AF: 0.000597 AC: 91 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.000725 AC XY: 54 AN XY: 74468

African (AFR) AF: 0.0000962 AC: 4 AN: 41588

American (AMR) AF: 0.00131 AC: 20 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000904 Hom.: 2

Bravo AF: 0.000642

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000602 AC: 73

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000771

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	Benign	0.091
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.085
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.25	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.097
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.046	D
Polyphen		1.0	D
Vest4		0.11
MVP		0.52
MPC		1.0
ClinPred		0.088	T
GERP RS		2.5
Varity_R		0.11
gMVP		0.79
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs144921822; hg19: chr6-3850644;