X-77456823-G-T

Variant names:

• chrX-77456823-G-T
• rs41300245
• NM_003868.3:c.*301G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003868.3(FGF16):​c.*301G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 194,007 control chromosomes in the GnomAD database, including 57 homozygotes. There are 1,091 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 0.019 (22 hom., 618 hem., cov: 22)
  • Exomes 𝑓: 0.028 (35 hom. 473 hem.)
• Consequence: FGF16 NM_003868.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.903
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-77456823-G-T is Benign according to our data. Variant chrX-77456823-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1202014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0194 (2159/111518) while in subpopulation NFE AF = 0.0314 (1666/53091). AF 95% confidence interval is 0.0301. There are 22 homozygotes in GnomAd4. There are 618 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2159 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.*301G>T		3_prime_UTR	Exon 3 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.*301G>T		3_prime_UTR	Exon 3 of 3	ENSP00000399324.2	O43320
	ENSG00000295984	ENST00000734738.1		n.179+4383C>A		intron	N/A
	ENSG00000295984	ENST00000734739.1		n.45+4383C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2159 AN: 111467 Hom.: 22 Cov.: 22

Gnomad AFR AF: 0.00453

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.00495

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.00847

Gnomad NFE AF: 0.0314

Gnomad OTH AF: 0.0213

GnomAD4 exome AF: 0.0282 AC: 2326 AN: 82489 Hom.: 35 Cov.: 0 AF XY: 0.0356 AC XY: 473 AN XY: 13297

African (AFR) AF: 0.00460 AC: 15 AN: 3260

American (AMR) AF: 0.0174 AC: 65 AN: 3731

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 48 AN: 2699

East Asian (EAS) AF: 0.00 AC: 0 AN: 5542

South Asian (SAS) AF: 0.00567 AC: 22 AN: 3883

European-Finnish (FIN) AF: 0.0298 AC: 122 AN: 4094

Middle Eastern (MID) AF: 0.0242 AC: 8 AN: 331

European-Non Finnish (NFE) AF: 0.0359 AC: 1920 AN: 53441

Other (OTH) AF: 0.0229 AC: 126 AN: 5508

GnomAD4 genome AF: 0.0194 AC: 2159 AN: 111518 Hom.: 22 Cov.: 22 AF XY: 0.0183 AC XY: 618 AN XY: 33702

African (AFR) AF: 0.00452 AC: 139 AN: 30722

American (AMR) AF: 0.0142 AC: 149 AN: 10457

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 38 AN: 2638

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3543

South Asian (SAS) AF: 0.00497 AC: 13 AN: 2618

European-Finnish (FIN) AF: 0.0196 AC: 118 AN: 6027

Middle Eastern (MID) AF: 0.00930 AC: 2 AN: 215

European-Non Finnish (NFE) AF: 0.0314 AC: 1666 AN: 53091

Other (OTH) AF: 0.0210 AC: 32 AN: 1522

Alfa AF: 0.0283 Hom.: 157

Bravo AF: 0.0190

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.77
DANN	Benign	0.53
PhyloP100		-0.90

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: rs41300245; hg19: chrX-76712314;