8-7296399-T-C

Variant names:

• chr8-7296399-T-C
• rs201746613
• ENST00000528221.1:c.432+2T>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001423532.1(FAM90A20):​c.432+2T>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 741,910 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0013 (25 hom., cov: 25)
  • Exomes 𝑓: 0.0012 (83 hom.)
• Consequence: FAM90A20 NM_001423532.1 splice_donor, intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.653

Genes affected

FAM90A20P (HGNC:32268): (family with sequence similarity 90 member A20) FAM90A20 belongs to subfamily II of the primate-specific FAM90A gene family, which originated from multiple duplications and rearrangements (Bosch et al., 2007 [PubMed 17684299]). For background information on the FAM90A gene family, as well as information on the evolution of FAM90A genes, see FAM90A1 (MIM 613041).[supplied by OMIM, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High Homozygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM90A20	NM_001423532.1	c.432+2T>C		splice_donor_variant, intron_variant	Intron 3 of 3		NP_001410461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM90A20P	ENST00000528221.1	c.432+2T>C		splice_donor_variant, intron_variant	Intron 3 of 3	6		ENSP00000514265.1

Frequencies

GnomAD3 genomes AF: 0.00128 AC: 172 AN: 134242 Hom.: 25 Cov.: 25

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000484

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.000612

Gnomad SAS AF: 0.000881

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.00259

GnomAD3 exomes AF: 0.00131 AC: 304 AN: 232152 Hom.: 58 AF XY: 0.00115 AC XY: 146 AN XY: 126768

Gnomad AFR exome AF: 0.00184

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00204

Gnomad EAS exome AF: 0.00185

Gnomad SAS exome AF: 0.00115

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00134

Gnomad OTH exome AF: 0.00190

GnomAD4 exome AF: 0.00119 AC: 721 AN: 607604 Hom.: 83 Cov.: 6 AF XY: 0.00122 AC XY: 405 AN XY: 331602

Gnomad4 AFR exome AF: 0.00104

Gnomad4 AMR exome AF: 0.000806

Gnomad4 ASJ exome AF: 0.00166

Gnomad4 EAS exome AF: 0.00144

Gnomad4 SAS exome AF: 0.00121

Gnomad4 FIN exome AF: 0.0000195

Gnomad4 NFE exome AF: 0.00134

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.00129 AC: 173 AN: 134306 Hom.: 25 Cov.: 25 AF XY: 0.00106 AC XY: 70 AN XY: 65734

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.000553

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.000614

Gnomad4 SAS AF: 0.000882

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00179

Gnomad4 OTH AF: 0.00256

Alfa AF: 0.00316 Hom.: 16

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	14
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201746613; hg19: chr8-7153921;