Variant 6-3849891-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_012135.3(FAM50B):c.80A>T(p.Gln27Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FAM50B
NM_012135.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3211667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM50B	NM_012135.3 linkuse as main transcript	c.80A>T	p.Gln27Leu	missense_variant	2/2	ENST00000648326.1	NP_036267.1	Q9Y247A0A024QZY3
FAM50B	XM_017010729.2 linkuse as main transcript	c.80A>T	p.Gln27Leu	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.80A>T	p.Gln27Leu	missense_variant	2/2		NM_012135.3	ENSP00000496837.1	Q9Y247
FAM50B	ENST00000380274.2 linkuse as main transcript	c.80A>T	p.Gln27Leu	missense_variant	1/1	6		ENSP00000369627.1	Q9Y247
ENSG00000238158	ENST00000454396.2 linkuse as main transcript	n.80-5579A>T		intron_variant		5
ENSG00000233068	ENST00000648025.1 linkuse as main transcript	n.76+17880A>T		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250540

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461428

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 17, 2024

The c.80A>T (p.Q27L) alteration is located in exon 2 (coding exon 1) of the FAM50B gene. This alteration results from a A to T substitution at nucleotide position 80, causing the glutamine (Q) at amino acid position 27 to be replaced by a leucine (L). 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

0.27

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.90

.;.;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.9

.;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.012

.;D;D

Sift4G

Uncertain

0.014

.;D;D

Polyphen

0.57

P;P;P

Vest4

0.36, 0.39

MutPred

0.16

Loss of methylation at K32 (P = 0.0701);Loss of methylation at K32 (P = 0.0701);Loss of methylation at K32 (P = 0.0701);

MVP

0.65

MPC

1.3

ClinPred

0.94

GERP RS

4.2

Varity_R

0.40

gMVP

0.97

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