NM_003868.3:c.379-209C>T

Variant names:

• chrX-77456068-C-T
• rs146784489
• NM_003868.3:c.379-209C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003868.3(FGF16):​c.379-209C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 112,337 control chromosomes in the GnomAD database, including 2 homozygotes. There are 169 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0052 (2 hom., 169 hem., cov: 23)
• Consequence: FGF16 NM_003868.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.971
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant X-77456068-C-T is Benign according to our data. Variant chrX-77456068-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1216118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00522 (586/112337) while in subpopulation AFR AF = 0.0166 (513/30908). AF 95% confidence interval is 0.0154. There are 2 homozygotes in GnomAd4. There are 169 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High AC in GnomAd4 at 586 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.379-209C>T		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.379-209C>T		intron	N/A	ENSP00000399324.2	O43320
	ENSG00000295984	ENST00000734738.1		n.179+5138G>A		intron	N/A
	ENSG00000295984	ENST00000734739.1		n.45+5138G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00517 AC: 581 AN: 112283 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00370

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000469

Gnomad OTH AF: 0.00727

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00522 AC: 586 AN: 112337 Hom.: 2 Cov.: 23 AF XY: 0.00490 AC XY: 169 AN XY: 34509

African (AFR) AF: 0.0166 AC: 513 AN: 30908

American (AMR) AF: 0.00262 AC: 28 AN: 10667

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3565

South Asian (SAS) AF: 0.00334 AC: 9 AN: 2695

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000469 AC: 25 AN: 53287

Other (OTH) AF: 0.00718 AC: 11 AN: 1533

Alfa AF: 0.00227 Hom.: 12

Bravo AF: 0.00593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.60
PhyloP100		0.97

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: rs146784489; hg19: chrX-76711559;