rs797045419

Positions:

• chrX-80690005-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The ENST00000373275.5(BRWD3):​c.3690A>G​(p.Ala1230=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,491 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: BRWD3 ENST00000373275.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.12

Genes affected

BRWD3 (HGNC:17342): (bromodomain and WD repeat domain containing 3) The protein encoded by this gene contains a bromodomain and several WD repeats. It is thought to have a chromatin-modifying function, and may thus play a role in transcription. Mutations in this gene are associated with a spectrum of cognitive disabilities and X-linked macrocephaly. This gene is also associated with translocations in patients with B-cell chronic lymphocytic leukemia. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant X-80690005-T-C is Benign according to our data. Variant chrX-80690005-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210541.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
• BP7: Synonymous conserved (PhyloP=1.12 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRWD3	NM_153252.5	c.3690A>G	p.Ala1230=	synonymous_variant	32/41	ENST00000373275.5	NP_694984.5
BRWD3	XM_005262113.4	c.3540A>G	p.Ala1180=	synonymous_variant	31/40		XP_005262170.1
BRWD3	XM_017029384.2	c.2478A>G	p.Ala826=	synonymous_variant	21/30		XP_016884873.1
BRWD3	XM_047441957.1	c.3690A>G	p.Ala1230=	synonymous_variant	32/38		XP_047297913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRWD3	ENST00000373275.5	c.3690A>G	p.Ala1230=	synonymous_variant	32/41	1	NM_153252.5	ENSP00000362372	P1
BRWD3	ENST00000473691.1	n.1826A>G		non_coding_transcript_exon_variant	16/25	2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.0000110 AC: 2 AN: 182604 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67292

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000732

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: 0.00

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1095491 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 361387

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000569

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000332

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 17, 2014

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.74

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: rs797045419; hg19: chrX-79945504;