rs763202512

Positions:

• chr13-36819475-G-GCGGCCT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM4 BP6_Moderate

The NM_000538.4(RFXAP):​c.120_125dupGGCCTC​(p.Ser42_Gln43insAlaSer) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,518,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: RFXAP NM_000538.4 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.998

Genes affected

RFXAP (HGNC:9988): (regulatory factor X associated protein) Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated ankyrin-containing protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. Once bound to the promoter, this complex associates with the non-DNA-binding factor MHC class II transactivator, which controls the cell type specificity and inducibility of MHC class II gene expression. Mutations in this gene have been linked to bare lymphocyte syndrome type II, complementation group D. Transcript variants utilizing different polyA signals have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000538.4.
• BP6: Variant 13-36819475-G-GCGGCCT is Benign according to our data. Variant chr13-36819475-G-GCGGCCT is described in ClinVar as [Likely_benign]. Clinvar id is 538587.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFXAP	NM_000538.4	c.120_125dupGGCCTC	p.Ser42_Gln43insAlaSer	disruptive_inframe_insertion	1/3	ENST00000255476.3	NP_000529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFXAP	ENST00000255476.3	c.120_125dupGGCCTC	p.Ser42_Gln43insAlaSer	disruptive_inframe_insertion	1/3	1	NM_000538.4	ENSP00000255476.3

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000299 AC: 38 AN: 127190 Hom.: 0 AF XY: 0.000255 AC XY: 18 AN XY: 70488

Gnomad AFR exome AF: 0.000201

Gnomad AMR exome AF: 0.0000973

Gnomad ASJ exome AF: 0.00266

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000487

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.000293

GnomAD4 exome AF: 0.000435 AC: 595 AN: 1366690 Hom.: 0 Cov.: 31 AF XY: 0.000429 AC XY: 289 AN XY: 673710

Gnomad4 AFR exome AF: 0.000134

Gnomad4 AMR exome AF: 0.000218

Gnomad4 ASJ exome AF: 0.00315

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000402

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000436

Gnomad4 OTH exome AF: 0.000693

GnomAD4 genome AF: 0.000375 AC: 57 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74392

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000695 Hom.: 1

Bravo AF: 0.000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class II deficiency Benign:1 Other:1

not provided, no classification provided	phenotyping only	GenomeConnect - Invitae Patient Insights Network	-	Variant classified as Likely benign and reported on 01-24-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

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: rs763202512; hg19: chr13-37393612;