X-9027858-T-C

Position:

• chrX-9027858-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_205849.3(FAM9B):​c.492+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,187,359 control chromosomes in the GnomAD database, including 2 homozygotes. There are 927 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., 34 hem., cov: 23)
  • Exomes 𝑓: 0.0027 (2 hom. 893 hem.)
• Consequence: FAM9B NM_205849.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.138

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-9027858-T-C is Benign according to our data. Variant chrX-9027858-T-C is described in ClinVar as [Benign]. Clinvar id is 784729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM9B	NM_205849.3	c.492+10A>G		intron_variant		ENST00000327220.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM9B	ENST00000327220.10	c.492+10A>G		intron_variant		1	NM_205849.3	P1

Frequencies

GnomAD3 genomes AF: 0.00144 AC: 162 AN: 112200 Hom.: 0 Cov.: 23 AF XY: 0.000990 AC XY: 34 AN XY: 34342

Gnomad AFR AF: 0.000388

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000475

Gnomad ASJ AF: 0.000377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000328

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00263

Gnomad OTH AF: 0.00132

GnomAD3 exomes AF: 0.00126 AC: 231 AN: 182873 Hom.: 0 AF XY: 0.00137 AC XY: 92 AN XY: 67389

Gnomad AFR exome AF: 0.000532

Gnomad AMR exome AF: 0.000219

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000188

Gnomad NFE exome AF: 0.00261

Gnomad OTH exome AF: 0.000443

GnomAD4 exome AF: 0.00272 AC: 2923 AN: 1075105 Hom.: 2 Cov.: 25 AF XY: 0.00260 AC XY: 893 AN XY: 343369

Gnomad4 AFR exome AF: 0.000502

Gnomad4 AMR exome AF: 0.000256

Gnomad4 ASJ exome AF: 0.000104

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000890

Gnomad4 NFE exome AF: 0.00336

Gnomad4 OTH exome AF: 0.00223

GnomAD4 genome AF: 0.00144 AC: 162 AN: 112254 Hom.: 0 Cov.: 23 AF XY: 0.000988 AC XY: 34 AN XY: 34406

Gnomad4 AFR AF: 0.000387

Gnomad4 AMR AF: 0.000474

Gnomad4 ASJ AF: 0.000377

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000328

Gnomad4 NFE AF: 0.00263

Gnomad4 OTH AF: 0.00130

Alfa AF: 0.00153 Hom.: 12

Bravo AF: 0.00120

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs200052167; hg19: chrX-8995899;