NM_001079673.2:c.742G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001079673.2(FNDC3A):​c.742G>A​(p.Val248Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V248F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FNDC3A NM_001079673.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B: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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052788645).
• BP6: Variant 13-49136583-G-A is Benign according to our data. Variant chr13-49136583-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2208752.Status of the report is criteria_provided_single_submitter, 1 stars.

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>A	p.Val248Ile	missense	Exon 6 of 26	NP_001073141.1	Q9Y2H6-1
	FNDC3A	NM_001278438.2		c.742G>A	p.Val248Ile	missense	Exon 6 of 26	NP_001265367.1	Q9Y2H6-1
	FNDC3A	NM_014923.5		c.574G>A	p.Val192Ile	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>A	p.Val248Ile	missense	Exon 6 of 26	ENSP00000417257.1	Q9Y2H6-1
	FNDC3A	ENST00000541916.5	TSL:1	c.742G>A	p.Val248Ile	missense	Exon 6 of 26	ENSP00000441831.1	Q9Y2H6-1
	FNDC3A	ENST00000398316.7	TSL:1	c.574G>A	p.Val192Ile	missense	Exon 4 of 24	ENSP00000381362.3	Q9Y2H6-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460262 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726096

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

American (AMR) AF: 0.0000671 AC: 3 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: 0.00 AC: 0 AN: 1110620

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.089
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.046
Sift	Benign	0.19	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.073
MutPred		0.34		Gain of catalytic residue at K243 (P = 0.0078)
MVP		0.093
MPC		0.17
ClinPred		0.027	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.019
gMVP		0.063
Mutation Taster		=96/4	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;