3-172251287-C-T

Position:

• chr3-172251287-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022763.4(FNDC3B):​c.536C>T​(p.Thr179Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T179S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FNDC3B NM_022763.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11

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 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=0.2524916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNDC3B	NM_022763.4	c.536C>T	p.Thr179Ile	missense_variant	6/26	ENST00000415807.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNDC3B	ENST00000415807.7	c.536C>T	p.Thr179Ile	missense_variant	6/26	1	NM_022763.4	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459982 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726426

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;D;D;T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.4	N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.032	D;D;D;D
Polyphen		0.0020	B;B;B;.
Vest4		0.067
MutPred		0.39		Gain of catalytic residue at T179 (P = 0.0424);Gain of catalytic residue at T179 (P = 0.0424);Gain of catalytic residue at T179 (P = 0.0424);.;
MVP		0.10
MPC		0.30
ClinPred		0.63	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs7652177; hg19: chr3-171969077;