rs3993757

Variant names:

• chr6-31622969-C-A
• rs3993757
• NM_004638.4:c.112+68C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31622969-C-A
• chr6-31622969-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004638.4(PRRC2A):​c.112+68C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000873 in 1,145,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 0 publications found

Genes affected

PRRC2A (HGNC:13918): (proline rich coiled-coil 2A) A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. This gene has microsatellite repeats which are associated with the age-at-onset of insulin-dependent diabetes mellitus (IDDM) and possibly thought to be involved with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. This gene is also a candidate gene for the development of rheumatoid arthritis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2010]

ENSG00000291302 (HGNC:):

SNORA38 (HGNC:32631): (small nucleolar RNA, H/ACA box 38)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.112+68C>A		intron_variant	Intron 2 of 30	ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.112+68C>A		intron_variant	Intron 2 of 30		NP_542417.2
PRRC2A	XM_047419336.1	c.112+68C>A		intron_variant	Intron 2 of 29		XP_047275292.1
SNORA38	NR_002971.1	n.-110C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.112+68C>A		intron_variant	Intron 2 of 30	1	NM_004638.4	ENSP00000365201.2
ENSG00000291302	ENST00000706625.1	c.*109C>A		downstream_gene_variant				ENSP00000516471.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.73e-7 AC: 1 AN: 1145700 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 585364

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26904

American (AMR) AF: 0.00 AC: 0 AN: 42858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24126

East Asian (EAS) AF: 0.00 AC: 0 AN: 38222

South Asian (SAS) AF: 0.00 AC: 0 AN: 79500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5172

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 825812

Other (OTH) AF: 0.00 AC: 0 AN: 50114

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.33
DANN	Benign	0.74
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3993757; hg19: chr6-31590746;