13-49136583-G-T

Variant names:

• chr13-49136583-G-T
• rs1882375899
• NM_001079673.2:c.742G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001079673.2(FNDC3A):​c.742G>T​(p.Val248Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V248I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FNDC3A NM_001079673.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04
• Publications: 0 publications found

Genes affected

FNDC3A (HGNC:20296): (fibronectin type III domain containing 3A) Enables RNA binding activity. Predicted to act upstream of or within several processes, including Sertoli cell development; fertilization; and spermatid development. Located in Golgi apparatus. [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=0.07956919).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079673.2. 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
	FNDC3A	NM_001079673.2	MANE Select	c.742G>T	p.Val248Phe	missense	Exon 6 of 26	NP_001073141.1	Q9Y2H6-1
	FNDC3A	NM_001278438.2		c.742G>T	p.Val248Phe	missense	Exon 6 of 26	NP_001265367.1	Q9Y2H6-1
	FNDC3A	NM_014923.5		c.574G>T	p.Val192Phe	missense	Exon 4 of 24	NP_055738.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNDC3A	ENST00000492622.6	TSL:1 MANE Select	c.742G>T	p.Val248Phe	missense	Exon 6 of 26	ENSP00000417257.1	Q9Y2H6-1
	FNDC3A	ENST00000541916.5	TSL:1	c.742G>T	p.Val248Phe	missense	Exon 6 of 26	ENSP00000441831.1	Q9Y2H6-1
	FNDC3A	ENST00000398316.7	TSL:1	c.574G>T	p.Val192Phe	missense	Exon 4 of 24	ENSP00000381362.3	Q9Y2H6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460262 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726096

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44706

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110620

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.0
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.046
Sift	Benign	0.049	D
Sift4G	Benign	0.23	T
Polyphen		0.0060	B
Vest4		0.26
MutPred		0.36		Gain of catalytic residue at K243 (P = 0.0074)
MVP		0.15
MPC		0.30
ClinPred		0.092	T
GERP RS		1.1
Varity_R		0.057
gMVP		0.18
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1882375899; hg19: chr13-49710719;