X-77447842-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate 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: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.243

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]

ACMG classification

Verdict is Benign. Variant got -15 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 [Likely_benign]. Clinvar id is 1218399.Status of the report is criteria_provided_single_submitter, 1 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF16	NM_003868.3	c.168A>G	p.Leu56Leu	synonymous_variant	Exon 1 of 3	ENST00000439435.3	NP_003859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF16	ENST00000439435.3	c.168A>G	p.Leu56Leu	synonymous_variant	Exon 1 of 3	1	NM_003868.3	ENSP00000399324.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 112015 AN: 112513 Hom.: 38588 Cov.: 25 AF XY: 0.996 AC XY: 34495 AN XY: 34647 FAILED QC

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

Gnomad4 AFR exome AF: 0.999

Gnomad4 AMR exome AF: 0.999

Gnomad4 ASJ exome AF: 0.992

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.990

Gnomad4 FIN exome AF: 0.996

Gnomad4 NFE exome AF: 0.993

Gnomad4 OTH exome AF: 0.996

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

Gnomad4 AFR AF: 0.999

Gnomad4 AMR AF: 0.999

Gnomad4 ASJ AF: 0.991

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.987

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.993

Gnomad4 OTH AF: 0.997

Alfa AF: 0.995 Hom.: 6974

Bravo AF: 0.996

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 30, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1054967228; hg19: -;