Genetic Variant FAM50B:p.Lys116Asn (chr6-3850159-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012135.3(FAM50B):c.348G>C(p.Lys116Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,612,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

FAM50B
NM_012135.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.084288806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM50B	NM_012135.3 link	c.348G>C	p.Lys116Asn	missense_variant	Exon 2 of 2	ENST00000648326.1	NP_036267.1	Q9Y247A0A024QZY3
FAM50B	XM_017010729.2 link	c.348G>C	p.Lys116Asn	missense_variant	Exon 2 of 2		XP_016866218.1	Q9Y247A0A024QZY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM50B	ENST00000648326.1 link	c.348G>C	p.Lys116Asn	missense_variant	Exon 2 of 2		NM_012135.3	ENSP00000496837.1	Q9Y247
FAM50B	ENST00000380274.2 link	c.348G>C	p.Lys116Asn	missense_variant	Exon 1 of 1	6		ENSP00000369627.1	Q9Y247
ENSG00000238158	ENST00000454396.2 link	n.80-5311G>C		intron_variant	Intron 1 of 1	5
ENSG00000233068	ENST00000648025.1 link	n.76+18148G>C		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000771

AC:

AN:

246542

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

134010

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000205

AC:

299

AN:

1460716

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

148

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000907

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.348G>C (p.K116N) alteration is located in exon 2 (coding exon 1) of the FAM50B gene. This alteration results from a G to C substitution at nucleotide position 348, causing the lysine (K) at amino acid position 116 to be replaced by an asparagine (N). 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.084

T;T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.92

.;.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.7

.;D;D

REVEL

Benign

0.090

Sift

Benign

0.036

.;D;D

Sift4G

Uncertain

0.038

.;D;D

Polyphen

0.026

B;B;B

Vest4

0.10, 0.11

MutPred

0.42

Loss of methylation at K116 (P = 0.0046);Loss of methylation at K116 (P = 0.0046);Loss of methylation at K116 (P = 0.0046);

MVP

0.25

MPC

1.4

ClinPred

0.051

GERP RS

3.4

Varity_R

0.22

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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