rs1054967228

Variant names:

• chrX-77447842-A-G
• rs1054967228
• NM_003868.3:c.168A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003868.3(FGF16):​c.168A>G​(p.Leu56Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (38583 hom., 34556 hem., cov: 25)
  • Exomes 𝑓: 0.99 (60101 hom. 62145 hem.)
  • Failed GnomAD Quality Control
• Consequence: FGF16 NM_003868.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.243
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=10.36).
• BP6: Variant X-77447842-A-G is Benign according to our data. Variant chrX-77447842-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1218399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.243 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

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.168A>G	p.Leu56Leu	synonymous	Exon 1 of 3	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.168A>G	p.Leu56Leu	synonymous	Exon 1 of 3	ENSP00000399324.2	O43320
	ENSG00000295984	ENST00000734738.1		n.179+13364T>C		intron	N/A
	ENSG00000295984	ENST00000734739.1		n.45+13364T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.996 AC: 112015 AN: 112513 Hom.: 38588 Cov.: 25

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.986

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.996

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.997

GnomAD4 exome AF: 0.994 AC: 183031 AN: 184098 Hom.: 60101 Cov.: 0 AF XY: 0.994 AC XY: 62145 AN XY: 62524

African (AFR) AF: 0.999 AC: 5605 AN: 5610

American (AMR) AF: 0.999 AC: 5638 AN: 5644

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 6634 AN: 6689

East Asian (EAS) AF: 1.00 AC: 17430 AN: 17430

South Asian (SAS) AF: 0.990 AC: 2166 AN: 2188

European-Finnish (FIN) AF: 0.996 AC: 15884 AN: 15944

Middle Eastern (MID) AF: 0.990 AC: 909 AN: 918

European-Non Finnish (NFE) AF: 0.993 AC: 116244 AN: 117099

Other (OTH) AF: 0.996 AC: 12521 AN: 12576

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.996 AC: 112065 AN: 112563 Hom.: 38583 Cov.: 25 AF XY: 0.996 AC XY: 34556 AN XY: 34707

African (AFR) AF: 0.999 AC: 31106 AN: 31122

American (AMR) AF: 0.999 AC: 10772 AN: 10783

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 2622 AN: 2647

East Asian (EAS) AF: 1.00 AC: 3520 AN: 3520

South Asian (SAS) AF: 0.987 AC: 2654 AN: 2690

European-Finnish (FIN) AF: 0.997 AC: 6166 AN: 6186

Middle Eastern (MID) AF: 0.991 AC: 217 AN: 219

European-Non Finnish (NFE) AF: 0.993 AC: 52809 AN: 53193

Other (OTH) AF: 0.997 AC: 1521 AN: 1525

Alfa AF: 0.995 Hom.: 6974

Bravo AF: 0.996

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	10
PhyloP100		-0.24
PromoterAI		-0.022	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1054967228;