NM_000538.4:c.51C>T

Variant names:

• chr13-36819408-C-T
• rs2138212292
• NM_000538.4:c.51C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000538.4(RFXAP):​c.51C>T​(p.Gly17Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RFXAP NM_000538.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.489
• Publications: 0 publications found

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]

RFXAP Gene-Disease associations (from GenCC):

• MHC class II deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ENSG00000309469 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 13-36819408-C-T is Benign according to our data. Variant chr13-36819408-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1057973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.489 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000538.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFXAP	NM_000538.4	MANE Select	c.51C>T	p.Gly17Gly	synonymous	Exon 1 of 3	NP_000529.1	O00287

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFXAP	ENST00000255476.3	TSL:1 MANE Select	c.51C>T	p.Gly17Gly	synonymous	Exon 1 of 3	ENSP00000255476.3	O00287
	ENSG00000309469	ENST00000841309.1		n.122+169G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000172 AC: 2 AN: 1162778 Hom.: 0 Cov.: 31 AF XY: 0.00000179 AC XY: 1 AN XY: 558720

African (AFR) AF: 0.0000428 AC: 1 AN: 23378

American (AMR) AF: 0.00 AC: 0 AN: 8980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15434

East Asian (EAS) AF: 0.00 AC: 0 AN: 27350

South Asian (SAS) AF: 0.00 AC: 0 AN: 32702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33746

Middle Eastern (MID) AF: 0.000290 AC: 1 AN: 3450

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 970262

Other (OTH) AF: 0.00 AC: 0 AN: 47476

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MHC class II deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.5
DANN	Benign	0.88
PhyloP100		-0.49
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs2138212292; hg19: chr13-37393545;