Genetic Variant TLCD3B:p.Arg30Cys (chr16-30030440-G-A) – 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_031478.6(TLCD3B):c.88C>T(p.Arg30Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,603,326 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: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

TLCD3B
NM_031478.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.641

Variant links:

Genes affected

TLCD3B (HGNC:25295): (TLC domain containing 3B) This gene encodes a transmembrane protein, which may be a likely target of peroxisome proliferator-activated receptor gamma (PPAR-gamma). The product of the orthologous gene in mouse is related to obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TLCD3B 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=0.23570746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD3B	NM_031478.6 link	c.88C>T	p.Arg30Cys	missense_variant	Exon 1 of 5	ENST00000380495.9	NP_113666.2	Q71RH2-1F1T0F5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TLCD3B	ENST00000380495.9 link	c.88C>T	p.Arg30Cys	missense_variant	Exon 1 of 5	1	NM_031478.6	ENSP00000369863.4	Q71RH2-1
TLCD3B	ENST00000561666.5 link	c.126-925C>T		intron_variant	Intron 5 of 6	5		ENSP00000456854.1	H3BST4
TLCD3B	ENST00000569508.6 link	n.*41-925C>T		intron_variant	Intron 2 of 3	5		ENSP00000457712.2	H3BUM7

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

236202

Hom.:

AF XY:

0.0000231

AC XY:

AN XY:

129790

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000373

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000441

AC:

AN:

1451004

Hom.:

Cov.:

AF XY:

0.0000388

AC XY:

AN XY:

721726

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000442

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000677

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000271

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.88C>T (p.R30C) alteration is located in exon 1 (coding exon 1) of the FAM57B gene. This alteration results from a C to T substitution at nucleotide position 88, causing the arginine (R) at amino acid position 30 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.0057

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.85

M_CAP

Benign

0.0036

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.45

Sift

Benign

0.041

Sift4G

Uncertain

0.051

Polyphen

0.99

Vest4

0.19

MVP

0.48

MPC

1.4

ClinPred

0.53

GERP RS

4.7

Varity_R

0.22

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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