chr3-172251439-A-G

Position:

• chr3-172251439-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022763.4(FNDC3B):​c.688A>G​(p.Ser230Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNDC3B NM_022763.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06688869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC3B	NM_022763.4	c.688A>G	p.Ser230Gly	missense_variant	6/26	ENST00000415807.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC3B	ENST00000415807.7	c.688A>G	p.Ser230Gly	missense_variant	6/26	1	NM_022763.4	P1

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

Dec 14, 2021

The c.688A>G (p.S230G) alteration is located in exon 6 (coding exon 5) of the FNDC3B gene. This alteration results from a A to G substitution at nucleotide position 688, causing the serine (S) at amino acid position 230 to be replaced by a glycine (G). 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	0.086
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T;T;T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.57	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.067	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N;N;N;.
MutationTaster	Benign	0.97	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.53	N;N;N;N
REVEL	Benign	0.034
Sift	Benign	0.44	T;T;T;T
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.011	B;B;B;.
Vest4		0.14
MutPred		0.24		Loss of phosphorylation at S230 (P = 0.0128);Loss of phosphorylation at S230 (P = 0.0128);Loss of phosphorylation at S230 (P = 0.0128);.;
MVP		0.47
MPC		0.25
ClinPred		0.15	T
GERP RS		0.32
Varity_R		0.10
gMVP		0.12

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: chr3-171969229;