Genetic Variant FNDC3A:p.Val39Ile (chr13-49075304-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001079673.2(FNDC3A):c.115G>A(p.Val39Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,447,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

FNDC3A
NM_001079673.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.98

Publications

0 publications found

Variant links:

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]

FNDC3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40579164).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FNDC3A	NM_001079673.2	MANE Select	c.115G>A	p.Val39Ile	missense	Exon 3 of 26	NP_001073141.1	Q9Y2H6-1
FNDC3A	NM_001278438.2		c.115G>A	p.Val39Ile	missense	Exon 3 of 26	NP_001265367.1	Q9Y2H6-1
FNDC3A	NR_103528.2		n.410G>A		non_coding_transcript_exon	Exon 3 of 26

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FNDC3A	ENST00000492622.6	TSL:1 MANE Select	c.115G>A	p.Val39Ile	missense	Exon 3 of 26	ENSP00000417257.1	Q9Y2H6-1
FNDC3A	ENST00000541916.5	TSL:1	c.115G>A	p.Val39Ile	missense	Exon 3 of 26	ENSP00000441831.1	Q9Y2H6-1
FNDC3A	ENST00000484074.5	TSL:1	n.115G>A		non_coding_transcript_exon	Exon 3 of 26	ENSP00000420275.1	G5E9X3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1447634

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

720984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33150

American (AMR)

AF:

0.00

AC:

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26008

East Asian (EAS)

AF:

0.00

AC:

AN:

39406

South Asian (SAS)

AF:

0.0000583

AC:

AN:

85698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099858

Other (OTH)

AF:

0.00

AC:

AN:

59892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.0075

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0093

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.7

PhyloP100

8.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.77

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.48

MutPred

0.43

Gain of catalytic residue at V34 (P = 8e-04)

MVP

0.50

MPC

0.33

ClinPred

0.91

GERP RS

5.9

Varity_R

0.32

gMVP

0.37

Mutation Taster

=83/17

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over