Genetic Variant FGF16:p.Lys178Asn (chrX-77456432-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003868.3(FGF16):c.534A>C(p.Lys178Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,207,391 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000019 ( 0 hom. 5 hem. )

Consequence

FGF16
NM_003868.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85

Variant links:

Genes affected

FGF16 (HGNC:3672): (fibroblast growth factor 16) This gene encodes a member of a family of proteins that are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene is expressed in cardiac cells and is required for proper heart development. Mutation in this gene was also observed in individuals with metacarpal 4-5 fusion. [provided by RefSeq, Mar 2014]

FGF16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20874459).

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF16	NM_003868.3 link	c.534A>C	p.Lys178Asn	missense_variant	Exon 3 of 3	ENST00000439435.3	NP_003859.1	O43320A0A7U3L5H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF16	ENST00000439435.3 link	c.534A>C	p.Lys178Asn	missense_variant	Exon 3 of 3	1	NM_003868.3	ENSP00000399324.2		O43320

Frequencies

GnomAD3 genomes

AF:

0.00000899

AC:

AN:

111290

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33486

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000221

AC:

AN:

181383

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67371

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1096101

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

361547

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:

0.000148

Gnomad4 NFE exome

AF:

0.0000179

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000899

AC:

AN:

111290

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FGF16: PP3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.21

PrimateAI

Pathogenic

0.87

Sift4G

Uncertain

0.0060

Polyphen

0.089

Vest4

0.36

MVP

0.16

ClinPred

0.18

GERP RS

2.8

Varity_R

0.33

gMVP

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over