Variant 3-172285975-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_022763.4(FNDC3B):c.840G>T(p.Glu280Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,457,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

FNDC3B
NM_022763.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

Variant links:

Genes affected

FNDC3B (HGNC:24670): (fibronectin type III domain containing 3B) Enables RNA binding activity. Predicted to act upstream of or within several processes, including negative regulation of osteoblast differentiation; substrate adhesion-dependent cell spreading; and type II pneumocyte differentiation. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

FNDC3B links:

FNDC3B (HGNC:):

FNDC3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12248564).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC3B	NM_022763.4 linkuse as main transcript	c.840G>T	p.Glu280Asp	missense_variant	7/26	ENST00000415807.7	NP_073600.3	Q53EP0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FNDC3B	ENST00000415807.7 linkuse as main transcript	c.840G>T	p.Glu280Asp	missense_variant	7/26	1	NM_022763.4	ENSP00000411242.2	Q53EP0-1
FNDC3B	ENST00000336824.8 linkuse as main transcript	c.840G>T	p.Glu280Asp	missense_variant	7/26	1		ENSP00000338523.4	Q53EP0-1
FNDC3B	ENST00000416957.5 linkuse as main transcript	c.840G>T	p.Glu280Asp	missense_variant	7/26	1		ENSP00000389094.1	Q53EP0-1
FNDC3B	ENST00000469491.5 linkuse as main transcript	n.981G>T		non_coding_transcript_exon_variant	7/16	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

250360

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

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:

0.000164

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457288

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

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

Nov 29, 2024

The c.840G>T (p.E280D) alteration is located in exon 7 (coding exon 6) of the FNDC3B gene. This alteration results from a G to T substitution at nucleotide position 840, causing the glutamic acid (E) at amino acid position 280 to be replaced by an aspartic acid (D). 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

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.082

T;T;T

Eigen

Benign

0.0028

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

.;.;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;L;L

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.44

T;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.025

B;B;B

Vest4

0.31

MutPred

0.28

Loss of ubiquitination at K281 (P = 0.0597);Loss of ubiquitination at K281 (P = 0.0597);Loss of ubiquitination at K281 (P = 0.0597);

MVP

0.49

MPC

0.26

ClinPred

0.078

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.22

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