rs3130071

Variant names:

• chr6-31626851-T-A
• rs3130071
• NM_004638.4:c.1062T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_004638.4(PRRC2A):​c.1062T>A​(p.Gly354Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,608,150 control chromosomes in the GnomAD database, including 627,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.91 (63830 hom., cov: 30)
  • Exomes 𝑓: 0.88 (563411 hom.)
• Consequence: PRRC2A NM_004638.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.02
• Publications: 41 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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 6-31626851-T-A is Benign according to our data. Variant chr6-31626851-T-A is described in ClinVar as Benign. ClinVar VariationId is 3060526.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004638.4. 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
	PRRC2A	NM_004638.4	MANE Select	c.1062T>A	p.Gly354Gly	synonymous	Exon 10 of 31	NP_004629.3
	PRRC2A	NM_080686.3		c.1062T>A	p.Gly354Gly	synonymous	Exon 10 of 31	NP_542417.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	ENST00000376033.3	TSL:1 MANE Select	c.1062T>A	p.Gly354Gly	synonymous	Exon 10 of 31	ENSP00000365201.2
	PRRC2A	ENST00000376007.8	TSL:1	c.1062T>A	p.Gly354Gly	synonymous	Exon 10 of 31	ENSP00000365175.4
	PRRC2A	ENST00000464890.1	TSL:2	n.489T>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139031 AN: 152076 Hom.: 63766 Cov.: 30

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.938

GnomAD2 exomes AF: 0.916 AC: 218713 AN: 238852 AF XY: 0.916

Gnomad AFR exome AF: 0.979

Gnomad AMR exome AF: 0.957

Gnomad ASJ exome AF: 0.973

Gnomad EAS exome AF: 0.997

Gnomad FIN exome AF: 0.867

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.908

GnomAD4 exome AF: 0.878 AC: 1278678 AN: 1455956 Hom.: 563411 Cov.: 61 AF XY: 0.881 AC XY: 637953 AN XY: 723796

African (AFR) AF: 0.980 AC: 32766 AN: 33440

American (AMR) AF: 0.956 AC: 41715 AN: 43644

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 25259 AN: 26006

East Asian (EAS) AF: 0.998 AC: 39544 AN: 39622

South Asian (SAS) AF: 0.972 AC: 83185 AN: 85610

European-Finnish (FIN) AF: 0.865 AC: 45339 AN: 52442

Middle Eastern (MID) AF: 0.956 AC: 5502 AN: 5756

European-Non Finnish (NFE) AF: 0.858 AC: 951616 AN: 1109216

Other (OTH) AF: 0.893 AC: 53752 AN: 60220

GnomAD4 genome AF: 0.914 AC: 139153 AN: 152194 Hom.: 63830 Cov.: 30 AF XY: 0.916 AC XY: 68150 AN XY: 74404

African (AFR) AF: 0.975 AC: 40504 AN: 41524

American (AMR) AF: 0.938 AC: 14325 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3363 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5164 AN: 5188

South Asian (SAS) AF: 0.975 AC: 4700 AN: 4822

European-Finnish (FIN) AF: 0.877 AC: 9288 AN: 10592

Middle Eastern (MID) AF: 0.962 AC: 281 AN: 292

European-Non Finnish (NFE) AF: 0.863 AC: 58697 AN: 68002

Other (OTH) AF: 0.939 AC: 1986 AN: 2114

Alfa AF: 0.883 Hom.: 44894

Bravo AF: 0.922

Asia WGS AF: 0.980 AC: 3409 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PRRC2A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.3
DANN	Benign	0.85
PhyloP100		1.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs3130071; hg19: chr6-31594628;