X-77454272-GTTTTTTTTTTTTTTTTTTTTT-GTTTTTTTTT

Variant names:

• chrX-77454272-GTTTTTTTTTTTT-G
• rs782034788
• NM_003868.3:c.378+31_378+42delTTTTTTTTTTTT

Variant summary

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

The NM_003868.3(FGF16):​c.378+31_378+42delTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000792 in 151,455 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. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000044 (0 hom., 1 hem., cov: 11)
  • Exomes 𝑓: 0.000095 (0 hom. 1 hem.)
• Consequence: FGF16 NM_003868.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

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)

ENSG00000295984 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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+31_378+42delTTTTTTTTTTTT		intron	N/A	NP_003859.1	O43320

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF16	ENST00000439435.3	TSL:1 MANE Select	c.378+13_378+24delTTTTTTTTTTTT		intron	N/A	ENSP00000399324.2	O43320
	ENSG00000295984	ENST00000734738.1		n.179+6922_179+6933delAAAAAAAAAAAA		intron	N/A
	ENSG00000295984	ENST00000734739.1		n.45+6922_45+6933delAAAAAAAAAAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000436 AC: 2 AN: 45911 Hom.: 0 Cov.: 11

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: 0.0000742

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000947 AC: 10 AN: 105544 Hom.: 0 AF XY: 0.0000333 AC XY: 1 AN XY: 30026

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 1527

American (AMR) AF: 0.000298 AC: 1 AN: 3354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2975

East Asian (EAS) AF: 0.00 AC: 0 AN: 2274

South Asian (SAS) AF: 0.00 AC: 0 AN: 13486

European-Finnish (FIN) AF: 0.000133 AC: 2 AN: 15084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 463

European-Non Finnish (NFE) AF: 0.0000978 AC: 6 AN: 61370

Other (OTH) AF: 0.000200 AC: 1 AN: 5011

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000316958), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000436 AC: 2 AN: 45911 Hom.: 0 Cov.: 11 AF XY: 0.000110 AC XY: 1 AN XY: 9101

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9951

American (AMR) AF: 0.00 AC: 0 AN: 3657

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1428

East Asian (EAS) AF: 0.00 AC: 0 AN: 1205

South Asian (SAS) AF: 0.00 AC: 0 AN: 542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1179

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 62

European-Non Finnish (NFE) AF: 0.0000742 AC: 2 AN: 26951

Other (OTH) AF: 0.00 AC: 0 AN: 570

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 186

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

Other links and lift over

dbSNP: rs782034788; hg19: chrX-76709763;