Genetic Variant FNDC1:p.Ala11Val (chr6-159169628-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032532.3(FNDC1):c.32C>T(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FNDC1
NM_032532.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.734

Publications

0 publications found

Variant links:

Genes affected

FNDC1 (HGNC:21184): (fibronectin type III domain containing 1) Predicted to act upstream of or within several processes, including cellular response to hypoxia; positive regulation of cardiac muscle cell apoptotic process; and positive regulation of protein phosphorylation. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

FNDC1 links:

FNDC1-AS1 (HGNC:55706): (FNDC1 antisense RNA 1)

FNDC1-AS1 links:

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ACMG classification

Classification was made for transcript

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=0.2243799).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032532.3. 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
	FNDC1	NM_032532.3	MANE Select	c.32C>T	p.Ala11Val	missense	Exon 1 of 23	NP_115921.2	Q4ZHG4-1
	FNDC1-AS1	NR_121668.1		n.196+184G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FNDC1	ENST00000297267.14	TSL:1 MANE Select	c.32C>T	p.Ala11Val	missense	Exon 1 of 23	ENSP00000297267.9	Q4ZHG4-1
FNDC1	ENST00000906655.1		c.32C>T	p.Ala11Val	missense	Exon 1 of 20	ENSP00000576714.1
FNDC1	ENST00000906656.1		c.32C>T	p.Ala11Val	missense	Exon 1 of 19	ENSP00000576715.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

990836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

467788

African (AFR)

AF:

0.00

AC:

AN:

19690

American (AMR)

AF:

0.00

AC:

AN:

5526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10388

East Asian (EAS)

AF:

0.00

AC:

AN:

16620

South Asian (SAS)

AF:

0.00

AC:

AN:

20152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2426

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

863506

Other (OTH)

AF:

0.00

AC:

AN:

36994

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.34

M_CAP

Benign

0.025

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PhyloP100

0.73

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.30

REVEL

Benign

0.082

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.18

MutPred

0.46

Loss of disorder (P = 0.0218)

MVP

0.52

MPC

0.16

ClinPred

0.65

GERP RS

3.1

PromoterAI

-0.091

Neutral

(source)

Varity_R

0.14

gMVP

0.29

Mutation Taster

=89/11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over