Genetic Variant FGF16:c.378+30_378+42delTTTTTTTTTTTTT (chrX-77454272-GTTTTTTTTTTTTT-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+30_378+42delTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 151,435 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.00024 ( 0 hom., 1 hem., cov: 11)

Exomes 𝑓: 0.00028 ( 0 hom. 2 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

new If you want to explore the variant's impact on the transcript NM_003868.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BS2

High AC in GnomAd4 at 11 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+30_378+42delTTTTTTTTTTTTT		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+25delTTTTTTTTTTTTT	intron	N/A	ENSP00000399324.2	O43320
ENSG00000295984	ENST00000734738.1		n.179+6921_179+6933delAAAAAAAAAAAAA	intron	N/A
ENSG00000295984	ENST00000734739.1		n.45+6921_45+6933delAAAAAAAAAAAAA	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000240

AC:

AN:

45911

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000547

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00185

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000186

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000284

AC:

AN:

105529

Hom.:

AF XY:

0.0000666

AC XY:

AN XY:

30011

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1527

American (AMR)

AF:

0.000596

AC:

AN:

3354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2975

East Asian (EAS)

AF:

0.00

AC:

AN:

2273

South Asian (SAS)

AF:

0.000371

AC:

AN:

13483

European-Finnish (FIN)

AF:

0.0000663

AC:

AN:

15084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

463

European-Non Finnish (NFE)

AF:

0.000326

AC:

AN:

61360

Other (OTH)

AF:

0.000399

AC:

AN:

5010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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:

0.000240

AC:

AN:

45906

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

9102

show subpopulations

African (AFR)

AF:

0.000301

AC:

AN:

9955

American (AMR)

AF:

0.000547

AC:

AN:

3654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1428

East Asian (EAS)

AF:

0.00

AC:

AN:

1198

South Asian (SAS)

AF:

0.00183

AC:

AN:

545

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1179

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000186

AC:

AN:

26952

Other (OTH)

AF:

0.00

AC:

AN:

571

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

186

Bravo

AF:

0.000174

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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X-77454272-GTTTTTTTTTTTTTTTTTTTTT-GTTTTTTTT

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