Variant 6-3850410-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

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. 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

Variant links:

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]

FAM50B links:

ENSG00000238158 (HGNC:):

ENSG00000238158 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012669772).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM50B	NM_012135.3 linkuse as main transcript	c.599C>T	p.Thr200Met	missense_variant	2/2	ENST00000648326.1	NP_036267.1	Q9Y247A0A024QZY3
FAM50B	XM_017010729.2 linkuse as main transcript	c.599C>T	p.Thr200Met	missense_variant	2/2		XP_016866218.1	Q9Y247A0A024QZY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM50B	ENST00000648326.1 linkuse as main transcript	c.599C>T	p.Thr200Met	missense_variant	2/2		NM_012135.3	ENSP00000496837.1	Q9Y247
FAM50B	ENST00000380274.2 linkuse as main transcript	c.599C>T	p.Thr200Met	missense_variant	1/1	6		ENSP00000369627.1	Q9Y247
ENSG00000238158	ENST00000454396.2 linkuse as main transcript	n.80-5060C>T		intron_variant		5
ENSG00000233068	ENST00000648025.1 linkuse as main transcript	n.76+18399C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000641

AC:

160

AN:

249732

Hom.:

AF XY:

0.000606

AC XY:

AN XY:

135350

show subpopulations

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 SAS exome

AF:

0.000589

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.:

Cov.:

AF XY:

0.000495

AC XY:

360

AN XY:

726862

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00609

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000305

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000597

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000958

Hom.:

Bravo

AF:

0.000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000602

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2022

The c.599C>T (p.T200M) alteration is located in exon 2 (coding exon 1) of the FAM50B gene. This alteration results from a C to T substitution at nucleotide position 599, causing the threonine (T) at amino acid position 200 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

0.085

Eigen_PC

Benign

-0.097

FATHMM_MKL

Benign

0.25

LIST_S2

Pathogenic

0.98

.;.;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.7

M;M;M

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.8

.;D;D

REVEL

Benign

0.097

Sift

Uncertain

0.017

.;D;D

Sift4G

Uncertain

0.046

.;D;D

Polyphen

1.0

D;D;D

Vest4

0.11, 0.12

MVP

0.52

MPC

1.0

ClinPred

0.088

GERP RS

2.5

Varity_R

0.11

gMVP

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over