chr3-172251287-C-T

Variant names:

• chr3-172251287-C-T
• rs7652177
• NM_022763.4:c.536C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 62 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2524916).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022763.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC3B	NM_022763.4	MANE Select	c.536C>T	p.Thr179Ile	missense	Exon 6 of 26	NP_073600.3
	FNDC3B	NM_001135095.2		c.536C>T	p.Thr179Ile	missense	Exon 6 of 26	NP_001128567.1	Q53EP0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC3B	ENST00000415807.7	TSL:1 MANE Select	c.536C>T	p.Thr179Ile	missense	Exon 6 of 26	ENSP00000411242.2	Q53EP0-1
	FNDC3B	ENST00000336824.8	TSL:1	c.536C>T	p.Thr179Ile	missense	Exon 6 of 26	ENSP00000338523.4	Q53EP0-1
	FNDC3B	ENST00000416957.5	TSL:1	c.536C>T	p.Thr179Ile	missense	Exon 6 of 26	ENSP00000389094.1	Q53EP0-1

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

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110456

Other (OTH) AF: 0.00 AC: 0 AN: 60308

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.20
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.032	D
Polyphen		0.0020	B
Vest4		0.067
MutPred		0.39		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
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs7652177; hg19: chr3-171969077;