rs7652177

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-172251287-C-G
• chr3-172251287-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_022763.4(FNDC3B):​c.536C>G​(p.Thr179Ser) variant causes a missense change. The variant allele was found at a frequency of 0.524 in 1,609,202 control chromosomes in the GnomAD database, including 226,650 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.61 (29755 hom., cov: 30)
  • Exomes 𝑓: 0.52 (196895 hom.)
• Consequence: FNDC3B NM_022763.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.4724999E-6).
• BP6: Variant 3-172251287-C-G is Benign according to our data. Variant chr3-172251287-C-G is described in ClinVar as Benign. ClinVar VariationId is 3060403.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

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>G	p.Thr179Ser	missense	Exon 6 of 26	NP_073600.3
	FNDC3B	NM_001135095.2		c.536C>G	p.Thr179Ser	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>G	p.Thr179Ser	missense	Exon 6 of 26	ENSP00000411242.2	Q53EP0-1
	FNDC3B	ENST00000336824.8	TSL:1	c.536C>G	p.Thr179Ser	missense	Exon 6 of 26	ENSP00000338523.4	Q53EP0-1
	FNDC3B	ENST00000416957.5	TSL:1	c.536C>G	p.Thr179Ser	missense	Exon 6 of 26	ENSP00000389094.1	Q53EP0-1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91957 AN: 151812 Hom.: 29701 Cov.: 30

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.559

GnomAD2 exomes AF: 0.542 AC: 135829 AN: 250802 AF XY: 0.534

Gnomad AFR exome AF: 0.867

Gnomad AMR exome AF: 0.534

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.512

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.502

Gnomad OTH exome AF: 0.516

GnomAD4 exome AF: 0.516 AC: 751299 AN: 1457272 Hom.: 196895 Cov.: 35 AF XY: 0.515 AC XY: 373649 AN XY: 725152

African (AFR) AF: 0.871 AC: 29060 AN: 33368

American (AMR) AF: 0.533 AC: 23800 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12909 AN: 26102

East Asian (EAS) AF: 0.434 AC: 17218 AN: 39646

South Asian (SAS) AF: 0.572 AC: 49270 AN: 86134

European-Finnish (FIN) AF: 0.514 AC: 27465 AN: 53404

Middle Eastern (MID) AF: 0.469 AC: 2697 AN: 5752

European-Non Finnish (NFE) AF: 0.503 AC: 557044 AN: 1108002

Other (OTH) AF: 0.529 AC: 31836 AN: 60210

GnomAD4 genome AF: 0.606 AC: 92070 AN: 151930 Hom.: 29755 Cov.: 30 AF XY: 0.606 AC XY: 44998 AN XY: 74222

African (AFR) AF: 0.857 AC: 35546 AN: 41468

American (AMR) AF: 0.532 AC: 8115 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1763 AN: 3464

East Asian (EAS) AF: 0.498 AC: 2575 AN: 5166

South Asian (SAS) AF: 0.561 AC: 2699 AN: 4814

European-Finnish (FIN) AF: 0.530 AC: 5574 AN: 10524

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33975 AN: 67948

Other (OTH) AF: 0.559 AC: 1177 AN: 2104

Alfa AF: 0.514 Hom.: 15489

Bravo AF: 0.616

TwinsUK AF: 0.501 AC: 1857

ALSPAC AF: 0.514 AC: 1981

ESP6500AA AF: 0.853 AC: 3758

ESP6500EA AF: 0.493 AC: 4236

ExAC AF: 0.550 AC: 66822

Asia WGS AF: 0.575 AC: 1999 AN: 3478

EpiCase AF: 0.483

EpiControl AF: 0.486

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FNDC3B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0000035	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.1	N
PhyloP100		4.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.13
Sift	Benign	0.76	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.020
MutPred		0.26		Gain of disorder (P = 0.0581)
MPC		0.25
ClinPred		0.014	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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; COSMIC: COSV61037879;