Variant chr1-108717923-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144937.3(FNDC7):c.229C>T(p.Pro77Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,424 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

FNDC7
NM_001144937.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40

Variant links:

Genes affected

FNDC7 (HGNC:26668): (fibronectin type III domain containing 7) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

FNDC7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNDC7	NM_001144937.3 linkuse as main transcript	c.229C>T	p.Pro77Ser	missense_variant	3/13	ENST00000370017.9	NP_001138409.1	Q5VTL7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNDC7	ENST00000370017.9 linkuse as main transcript	c.229C>T	p.Pro77Ser	missense_variant	3/13	5	NM_001144937.3	ENSP00000359034.3		Q5VTL7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399424

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.229C>T (p.P77S) alteration is located in exon 3 (coding exon 3) of the FNDC7 gene. This alteration results from a C to T substitution at nucleotide position 229, causing the proline (P) at amino acid position 77 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.0089

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.011

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.5

REVEL

Benign

0.25

Sift

Benign

0.23

Sift4G

Uncertain

0.013

Vest4

0.55

MutPred

0.30

Gain of glycosylation at P77 (P = 0.0099);

MVP

0.81

MPC

0.54

ClinPred

0.96

GERP RS

5.9

Varity_R

0.12

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over