rs369583924

Variant names:

• chr13-49136419-G-T
• rs369583924
• NM_001079673.2:c.578G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-49136419-G-T
• chr13-49136419-G-A

Variant summary

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

The NM_001079673.2(FNDC3A):​c.578G>T​(p.Arg193Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• 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: 7.94
• Publications: 6 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.578G>T	p.Arg193Leu	missense	Exon 6 of 26	NP_001073141.1	Q9Y2H6-1
	FNDC3A	NM_001278438.2		c.578G>T	p.Arg193Leu	missense	Exon 6 of 26	NP_001265367.1	Q9Y2H6-1
	FNDC3A	NM_014923.5		c.410G>T	p.Arg137Leu	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.578G>T	p.Arg193Leu	missense	Exon 6 of 26	ENSP00000417257.1	Q9Y2H6-1
	FNDC3A	ENST00000541916.5	TSL:1	c.578G>T	p.Arg193Leu	missense	Exon 6 of 26	ENSP00000441831.1	Q9Y2H6-1
	FNDC3A	ENST00000398316.7	TSL:1	c.410G>T	p.Arg137Leu	missense	Exon 4 of 24	ENSP00000381362.3	Q9Y2H6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251198 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727218

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	D
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.017	D
Polyphen		0.97	D
Vest4		0.81
MutPred		0.37		Loss of methylation at K198 (P = 0.0438)
MVP		0.52
MPC		0.87
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.48
gMVP		0.45
Mutation Taster		=59/41	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: rs369583924; hg19: chr13-49710555;