ENST00000528221.1:c.432+2T>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000528221.1(FAM90A20):​c.432+2T>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000074 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000033 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM90A20 ENST00000528221.1 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 0 publications found

Genes affected

FAM90A20 (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]

FAM66B (HGNC:28890): (family with sequence similarity 66 member B)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM90A20	NM_001423532.1	c.432+2T>A		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
FAM90A20	ENST00000528221.1	c.432+2T>A		splice_donor_variant, intron_variant	Intron 3 of 3	6		ENSP00000514265.1
FAM66B	ENST00000820789.1	n.762+27898A>T		intron_variant	Intron 5 of 5
FAM66B	ENST00000820790.1	n.193-2432A>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00000744 AC: 1 AN: 134452 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000329 AC: 2 AN: 608028 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 331822

African (AFR) AF: 0.00 AC: 0 AN: 12454

American (AMR) AF: 0.00 AC: 0 AN: 42186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20520

East Asian (EAS) AF: 0.00 AC: 0 AN: 34620

South Asian (SAS) AF: 0.00 AC: 0 AN: 68614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2434

European-Non Finnish (NFE) AF: 0.00000580 AC: 2 AN: 344678

Other (OTH) AF: 0.00 AC: 0 AN: 31244

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000744 AC: 1 AN: 134452 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 65738

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

African (AFR) AF: 0.00 AC: 0 AN: 27952

American (AMR) AF: 0.00 AC: 0 AN: 14460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 4904

South Asian (SAS) AF: 0.00 AC: 0 AN: 4540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65724

Other (OTH) AF: 0.00 AC: 0 AN: 1932

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	16
DANN	Benign	0.55
PhyloP100		0.65

Splicing

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

Other links and lift over

dbSNP: rs201746613; hg19: chr8-7153921;