chrX-77454272-GTTT-G

Variant names:

• chrX-77454272-GTTT-G
• rs782034788
• NM_003868.3:c.378+40_378+42delTTT

Variant summary

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

The NM_003868.3(FGF16):​c.378+40_378+42delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 146,806 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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., 0 hem., cov: 11)
  • Exomes 𝑓: 0.024 (0 hom. 0 hem.)
• Consequence: FGF16 NM_003868.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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+40_378+42delTTT		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+15delTTT		intron	N/A	ENSP00000399324.2	O43320
	ENSG00000295984	ENST00000734738.1		n.179+6931_179+6933delAAA		intron	N/A
	ENSG00000295984	ENST00000734739.1		n.45+6931_45+6933delAAA		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: 0.0241 AC: 2431 AN: 100900 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 27392

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

African (AFR) AF: 0.0223 AC: 33 AN: 1481

American (AMR) AF: 0.0327 AC: 106 AN: 3240

Ashkenazi Jewish (ASJ) AF: 0.0249 AC: 72 AN: 2895

East Asian (EAS) AF: 0.0334 AC: 73 AN: 2183

South Asian (SAS) AF: 0.0131 AC: 165 AN: 12639

European-Finnish (FIN) AF: 0.00903 AC: 134 AN: 14839

Middle Eastern (MID) AF: 0.0175 AC: 8 AN: 457

European-Non Finnish (NFE) AF: 0.0291 AC: 1696 AN: 58368

Other (OTH) AF: 0.0300 AC: 144 AN: 4798

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000436 AC: 2 AN: 45906 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 9102

⚠️ 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: 9955

American (AMR) AF: 0.00 AC: 0 AN: 3654

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 1198

South Asian (SAS) AF: 0.00 AC: 0 AN: 545

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 58

European-Non Finnish (NFE) AF: 0.0000742 AC: 2 AN: 26952

Other (OTH) AF: 0.00 AC: 0 AN: 571

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), 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		1.2

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

Other links and lift over

dbSNP: rs782034788; hg19: chrX-76709763;