Variant chr2-27494056-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022823.3(FNDC4):c.328G>A(p.Glu110Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FNDC4
NM_022823.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.18

Variant links:

Genes affected

FNDC4 (HGNC:20239): (fibronectin type III domain containing 4) Involved in response to transforming growth factor beta. Predicted to be located in endoplasmic reticulum and extracellular space. Predicted to be active in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FNDC4 links:

FNDC4 (HGNC:):

FNDC4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC4	NM_022823.3 linkuse as main transcript	c.328G>A	p.Glu110Lys	missense_variant	4/7	ENST00000264703.4	NP_073734.1	Q9H6D8
FNDC4	XM_047445471.1 linkuse as main transcript	c.328G>A	p.Glu110Lys	missense_variant	3/6		XP_047301427.1
FNDC4	XM_005264499.5 linkuse as main transcript	c.328G>A	p.Glu110Lys	missense_variant	4/6		XP_005264556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FNDC4	ENST00000264703.4 linkuse as main transcript	c.328G>A	p.Glu110Lys	missense_variant	4/7	1	NM_022823.3	ENSP00000264703.3	Q9H6D8
FNDC4	ENST00000476197.1 linkuse as main transcript	n.461G>A		non_coding_transcript_exon_variant	3/5	2
FNDC4	ENST00000491414.5 linkuse as main transcript	n.853G>A		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

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

Dec 13, 2022

The c.328G>A (p.E110K) alteration is located in exon 4 (coding exon 3) of the FNDC4 gene. This alteration results from a G to A substitution at nucleotide position 328, causing the glutamic acid (E) at amino acid position 110 to be replaced by a lysine (K). 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

0.40

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.79

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.7

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.30

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.74

MutPred

0.66

Gain of MoRF binding (P = 0.0128);

MVP

0.32

MPC

1.8

ClinPred

0.98

GERP RS

4.3

Varity_R

0.63

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over