X-9279959-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000651278.1(FAM9B):c.-355+15678A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 110,566 control chromosomes in the GnomAD database, including 13,597 homozygotes. There are 18,085 hemizygotes in GnomAD. 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 0.55 (13597 hom., 18085 hem., cov: 23)
• Consequence: FAM9B ENST00000651278.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

Genes affected

FAM9B (HGNC:18404): (family with sequence similarity 9 member B) This gene is a member of a gene family which arose through duplication on the X chromosome. The encoded protein may be localized to the nucleus as the protein contains several nuclear localization signals, and has similarity to a synaptonemal complex protein. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9B	ENST00000651278.1	c.-355+15678A>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 60789 AN: 110512 Hom.: 13602 Cov.: 23 AF XY: 0.550 AC XY: 18068 AN XY: 32848

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.607

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.570

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.550 AC: 60787 AN: 110566 Hom.: 13597 Cov.: 23 AF XY: 0.549 AC XY: 18085 AN XY: 32912

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.571

Alfa AF: 0.677 Hom.: 76975

Bravo AF: 0.526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.5
Dann	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1024443; hg19: chrX-9247999;