10-101770141-TAAAAAAAAAAAAAAA-TAAAAA

Variant names:

• chr10-101770141-TAAAAAAAAAA-T
• rs11322844
• NM_033163.5:c.*178_*187delTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_033163.5(FGF8):​c.*178_*187delTTTTTTTTTT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000294 in 272,288 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: FGF8 NM_033163.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86
• Publications: 1 publications found

Genes affected

FGF8 (HGNC:3686): (fibroblast growth factor 8) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein is known to be a factor that supports androgen and anchorage independent growth of mammary tumor cells. Overexpression of this gene has been shown to increase tumor growth and angiogensis. The adult expression of this gene is restricted to testes and ovaries. Temporal and spatial pattern of this gene expression suggests its function as an embryonic epithelial factor. Studies of the mouse and chick homologs revealed roles in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination. The alternative splicing of this gene results in four transcript variants. [provided by RefSeq, Jul 2008]

FGF8 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 6 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• holoprosencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000308881 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033163.5. 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
	FGF8	NM_033163.5	MANE Select	c.*178_*187delTTTTTTTTTT		3_prime_UTR	Exon 6 of 6	NP_149353.1	P55075-4
	FGF8	NM_033164.4		c.*178_*187delTTTTTTTTTT		3_prime_UTR	Exon 6 of 6	NP_149354.1	P55075-1
	FGF8	NM_006119.6		c.*178_*187delTTTTTTTTTT		3_prime_UTR	Exon 5 of 5	NP_006110.1	P55075-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF8	ENST00000320185.7	TSL:1 MANE Select	c.*178_*187delTTTTTTTTTT		3_prime_UTR	Exon 6 of 6	ENSP00000321797.2	P55075-4
	FGF8	ENST00000344255.8	TSL:1	c.*178_*187delTTTTTTTTTT		3_prime_UTR	Exon 6 of 6	ENSP00000340039.3	P55075-1
	FGF8	ENST00000469792.6	TSL:5	n.*877_*886delTTTTTTTTTT		splice_region non_coding_transcript_exon	Exon 5 of 5	ENSP00000473299.1	R4GMQ3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000294 AC: 8 AN: 272288 Hom.: 0 AF XY: 0.0000286 AC XY: 4 AN XY: 139814

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

African (AFR) AF: 0.00 AC: 0 AN: 7506

American (AMR) AF: 0.000102 AC: 1 AN: 9790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9076

East Asian (EAS) AF: 0.00 AC: 0 AN: 21674

South Asian (SAS) AF: 0.00 AC: 0 AN: 15132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1248

European-Non Finnish (NFE) AF: 0.0000350 AC: 6 AN: 171514

Other (OTH) AF: 0.0000601 AC: 1 AN: 16644

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000173310), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9

Splicing

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

Other links and lift over

dbSNP: rs11322844; hg19: chr10-103529898;