2-27494028-C-T

Position:

• chr2-27494028-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022823.3(FNDC4):​c.356G>A​(p.Arg119Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNDC4 NM_022823.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC4	NM_022823.3	c.356G>A	p.Arg119Lys	missense_variant	4/7	ENST00000264703.4
FNDC4	XM_047445471.1	c.356G>A	p.Arg119Lys	missense_variant	3/6
FNDC4	XM_005264499.5	c.356G>A	p.Arg119Lys	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC4	ENST00000264703.4	c.356G>A	p.Arg119Lys	missense_variant	4/7	1	NM_022823.3	P1
FNDC4	ENST00000476197.1	n.489G>A		non_coding_transcript_exon_variant	3/5	2
FNDC4	ENST00000491414.5	n.881G>A		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.356G>A (p.R119K) 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 356, causing the arginine (R) at amino acid position 119 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	Benign	0.20
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Benign	0.082
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.84	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.15
Sift	Benign	0.091	T
Sift4G	Uncertain	0.039	D
Polyphen		0.51	P
Vest4		0.55
MutPred		0.50		Gain of ubiquitination at R119 (P = 0.023);
MVP		0.48
MPC		0.81
ClinPred		0.70	D
GERP RS		5.2
Varity_R		0.32
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27716895;