Genetic Variant FGF16:c.378+28_378+42delTTTTTTTTTTTTTTT (chrX-77454272-GTTTTTTTTTTTTTTT-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003868.3(FGF16):c.378+28_378+42delTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 151,458 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., 1 hem., cov: 11)

Exomes 𝑓: 0.000047 ( 0 hom. 1 hem. )

Consequence

FGF16
NM_003868.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

syndactyly type 8
Inheritance: AD, XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

FGF16 links:

ENSG00000295984 (HGNC:):

ENSG00000295984 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 5 AD,XL gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003868.3. 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
	FGF16	NM_003868.3	MANE Select	c.378+28_378+42delTTTTTTTTTTTTTTT		intron	N/A	NP_003859.1	O43320

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FGF16	ENST00000439435.3	TSL:1 MANE Select	c.378+13_378+27delTTTTTTTTTTTTTTT	intron	N/A	ENSP00000399324.2	O43320
ENSG00000295984	ENST00000734738.1		n.179+6919_179+6933delAAAAAAAAAAAAAAA	intron	N/A
ENSG00000295984	ENST00000734739.1		n.45+6919_45+6933delAAAAAAAAAAAAAAA	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000218

AC:

AN:

45911

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000100

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000474

AC:

AN:

105547

Hom.:

AF XY:

0.0000333

AC XY:

AN XY:

30027

show subpopulations

African (AFR)

AF:

0.000655

AC:

AN:

1527

American (AMR)

AF:

0.000298

AC:

AN:

3355

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2975

East Asian (EAS)

AF:

0.00

AC:

AN:

2274

South Asian (SAS)

AF:

0.00

AC:

AN:

13486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

463

European-Non Finnish (NFE)

AF:

0.0000489

AC:

AN:

61373

Other (OTH)

AF:

0.00

AC:

AN:

5010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.0000218

AC:

AN:

45911

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

9101

show subpopulations

African (AFR)

AF:

0.000100

AC:

AN:

9951

American (AMR)

AF:

0.00

AC:

AN:

3657

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1428

East Asian (EAS)

AF:

0.00

AC:

AN:

1205

South Asian (SAS)

AF:

0.00

AC:

AN:

542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1179

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

26951

Other (OTH)

AF:

0.00

AC:

AN:

570

Age Distribution

Genome Hom

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

Alfa

AF:

0.00

Hom.:

186

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Splicing

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.

X-77454272-GTTTTTTTTTTTTTTTTTTTTT-GTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over