X-34943154-CGCCAGTACA-C

Variant names:

• chrX-34943154-CGCCAGTACA-C
• rs759524668
• NM_152631.3:c.329_337delTACAGCCAG

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM4 BP6 BS2

The NM_152631.3(FAM47B):​c.329_337delTACAGCCAG​(p.Val110_Pro112del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,210,101 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000071 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.00011 (0 hom. 26 hem.)
• Consequence: FAM47B NM_152631.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.10

Genes affected

FAM47B (HGNC:26659): (family with sequence similarity 47 member B)

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_152631.3.
• BP6: Variant X-34943154-CGCCAGTACA-C is Benign according to our data. Variant chrX-34943154-CGCCAGTACA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3054088.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47B	NM_152631.3	c.329_337delTACAGCCAG	p.Val110_Pro112del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000329357.6	NP_689844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47B	ENST00000329357.6	c.329_337delTACAGCCAG	p.Val110_Pro112del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_152631.3	ENSP00000328307.5

Frequencies

GnomAD3 genomes AF: 0.0000715 AC: 8 AN: 111911 Hom.: 0 Cov.: 22 AF XY: 0.0000587 AC XY: 2 AN XY: 34065

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000752

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000545 AC: 100 AN: 183394 Hom.: 0 AF XY: 0.000251 AC XY: 17 AN XY: 67836

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.000110 AC: 121 AN: 1098141 Hom.: 0 AF XY: 0.0000715 AC XY: 26 AN XY: 363521

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00341

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome AF: 0.0000715 AC: 8 AN: 111960 Hom.: 0 Cov.: 22 AF XY: 0.0000586 AC XY: 2 AN XY: 34126

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000751

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.000257

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FAM47B-related disorder Benign:1

May 27, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs759524668; hg19: chrX-34961271;