NM_003868.3:c.378+41_378+42delTT

Variant names:

• chrX-77454272-GTT-G
• rs782034788
• NM_003868.3:c.378+41_378+42delTT

Variant summary

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

The NM_003868.3(FGF16):​c.378+41_378+42delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 142,800 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: 0.048 (0 hom. 1 hem.)
• Consequence: FGF16 NM_003868.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.691
• 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+41_378+42delTT		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+14delTT		intron	N/A	ENSP00000399324.2	O43320
	ENSG00000295984	ENST00000734738.1		n.179+6932_179+6933delAA		intron	N/A
	ENSG00000295984	ENST00000734739.1		n.45+6932_45+6933delAA		intron	N/A

Frequencies

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

Gnomad AFR AF: 0.000100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000830

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

GnomAD2 exomes AF: 0.0207 AC: 491 AN: 23700 AF XY: 0.00

Gnomad AFR exome AF: 0.0277

Gnomad AMR exome AF: 0.0647

Gnomad ASJ exome AF: 0.0138

Gnomad EAS exome AF: 0.0592

Gnomad FIN exome AF: 0.000835

Gnomad NFE exome AF: 0.0166

Gnomad OTH exome AF: 0.0241

GnomAD4 exome AF: 0.0484 AC: 4689 AN: 96894 Hom.: 0 AF XY: 0.0000401 AC XY: 1 AN XY: 24932

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

African (AFR) AF: 0.0482 AC: 69 AN: 1431

American (AMR) AF: 0.0610 AC: 193 AN: 3162

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 104 AN: 2780

East Asian (EAS) AF: 0.0581 AC: 123 AN: 2118

South Asian (SAS) AF: 0.0315 AC: 373 AN: 11823

European-Finnish (FIN) AF: 0.0186 AC: 270 AN: 14516

Middle Eastern (MID) AF: 0.0418 AC: 18 AN: 431

European-Non Finnish (NFE) AF: 0.0585 AC: 3282 AN: 56093

Other (OTH) AF: 0.0566 AC: 257 AN: 4540

⚠️ 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

African (AFR) AF: 0.000100 AC: 1 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: 0.000835 AC: 1 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: 0.00 AC: 0 AN: 26952

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

Alfa AF: 0.00301 Hom.: 186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;