X-77454272-GT-G

Variant names:

• chrX-77454272-GT-G
• rs782034788
• NM_003868.3:c.378+42delT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_003868.3(FGF16):​c.378+42delT variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (1 hom., 0 hem., cov: 11)
  • Exomes 𝑓: 0.066 (1 hom. 2 hem.)
• Consequence: FGF16 NM_003868.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant X-77454272-GT-G is Benign according to our data. Variant chrX-77454272-GT-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1214792.Status of the report is criteria_provided_single_submitter, 1 stars.

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+42delT		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+13delT		intron	N/A	ENSP00000399324.2	O43320
	ENSG00000295984	ENST00000734738.1		n.179+6933delA		intron	N/A
	ENSG00000295984	ENST00000734739.1		n.45+6933delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00292 AC: 134 AN: 45899 Hom.: 1 Cov.: 11

Gnomad AFR AF: 0.00161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00109

Gnomad ASJ AF: 0.00350

Gnomad EAS AF: 0.00915

Gnomad SAS AF: 0.00369

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00356

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0278 AC: 658 AN: 23700 AF XY: 0.00

Gnomad AFR exome AF: 0.0373

Gnomad AMR exome AF: 0.0983

Gnomad ASJ exome AF: 0.0203

Gnomad EAS exome AF: 0.0854

Gnomad FIN exome AF: 0.00104

Gnomad NFE exome AF: 0.0201

Gnomad OTH exome AF: 0.0322

GnomAD4 exome AF: 0.0655 AC: 6383 AN: 97449 Hom.: 1 Cov.: 5 AF XY: 0.0000828 AC XY: 2 AN XY: 24141

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

African (AFR) AF: 0.0752 AC: 109 AN: 1449

American (AMR) AF: 0.0834 AC: 267 AN: 3203

Ashkenazi Jewish (ASJ) AF: 0.0596 AC: 167 AN: 2801

East Asian (EAS) AF: 0.0745 AC: 160 AN: 2147

South Asian (SAS) AF: 0.0449 AC: 524 AN: 11669

European-Finnish (FIN) AF: 0.0293 AC: 427 AN: 14598

Middle Eastern (MID) AF: 0.0622 AC: 27 AN: 434

European-Non Finnish (NFE) AF: 0.0767 AC: 4339 AN: 56539

Other (OTH) AF: 0.0788 AC: 363 AN: 4609

⚠️ 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: 0.00292 AC: 134 AN: 45894 Hom.: 1 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 9094

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

African (AFR) AF: 0.00161 AC: 16 AN: 9955

American (AMR) AF: 0.00109 AC: 4 AN: 3654

Ashkenazi Jewish (ASJ) AF: 0.00350 AC: 5 AN: 1428

East Asian (EAS) AF: 0.00921 AC: 11 AN: 1195

South Asian (SAS) AF: 0.00367 AC: 2 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: 0.00356 AC: 96 AN: 26943

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), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00415 Hom.: 186

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
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;