6-31628105-C-A

Variant names:

• chr6-31628105-C-A
• rs1046080
• NM_004638.4:c.1631C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004638.4(PRRC2A):​c.1631C>A​(p.Thr544Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 1,612,820 control chromosomes in the GnomAD database, including 455,099 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.74 (42349 hom., cov: 31)
  • Exomes 𝑓: 0.75 (412750 hom.)
• Consequence: PRRC2A NM_004638.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.78
• Publications: 78 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.3481995E-7).
• BP6: Variant 6-31628105-C-A is Benign according to our data. Variant chr6-31628105-C-A is described in ClinVar as Benign. ClinVar VariationId is 3060200.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 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.1631C>A	p.Thr544Lys	missense	Exon 12 of 31	NP_004629.3
	PRRC2A	NM_080686.3		c.1631C>A	p.Thr544Lys	missense	Exon 12 of 31	NP_542417.2	A0A1U9X974

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	ENST00000376033.3	TSL:1 MANE Select	c.1631C>A	p.Thr544Lys	missense	Exon 12 of 31	ENSP00000365201.2	P48634-1
	PRRC2A	ENST00000376007.8	TSL:1	c.1631C>A	p.Thr544Lys	missense	Exon 12 of 31	ENSP00000365175.4	P48634-1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112899 AN: 151872 Hom.: 42320 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.755

GnomAD2 exomes AF: 0.792 AC: 195889 AN: 247322 AF XY: 0.791

Gnomad AFR exome AF: 0.668

Gnomad AMR exome AF: 0.849

Gnomad ASJ exome AF: 0.892

Gnomad EAS exome AF: 0.980

Gnomad FIN exome AF: 0.803

Gnomad NFE exome AF: 0.746

Gnomad OTH exome AF: 0.778

GnomAD4 exome AF: 0.749 AC: 1093803 AN: 1460830 Hom.: 412750 Cov.: 93 AF XY: 0.751 AC XY: 545931 AN XY: 726722

African (AFR) AF: 0.667 AC: 22318 AN: 33476

American (AMR) AF: 0.840 AC: 37572 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 23236 AN: 26136

East Asian (EAS) AF: 0.982 AC: 39003 AN: 39700

South Asian (SAS) AF: 0.810 AC: 69831 AN: 86256

European-Finnish (FIN) AF: 0.796 AC: 41732 AN: 52404

Middle Eastern (MID) AF: 0.809 AC: 4666 AN: 5768

European-Non Finnish (NFE) AF: 0.728 AC: 809551 AN: 1111980

Other (OTH) AF: 0.760 AC: 45894 AN: 60386

GnomAD4 genome AF: 0.743 AC: 112972 AN: 151990 Hom.: 42349 Cov.: 31 AF XY: 0.750 AC XY: 55724 AN XY: 74274

African (AFR) AF: 0.667 AC: 27646 AN: 41430

American (AMR) AF: 0.769 AC: 11748 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3067 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5024 AN: 5162

South Asian (SAS) AF: 0.839 AC: 4039 AN: 4816

European-Finnish (FIN) AF: 0.816 AC: 8623 AN: 10564

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50205 AN: 67958

Other (OTH) AF: 0.759 AC: 1602 AN: 2110

Alfa AF: 0.754 Hom.: 185269

Bravo AF: 0.737

TwinsUK AF: 0.730 AC: 2705

ALSPAC AF: 0.719 AC: 2772

ESP6500AA AF: 0.684 AC: 2068

ESP6500EA AF: 0.743 AC: 4024

ExAC AF: 0.786 AC: 93014

Asia WGS AF: 0.904 AC: 3141 AN: 3478

EpiCase AF: 0.765

EpiControl AF: 0.767

ClinVar

ClinVar submissions

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
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.066	T
MetaRNN	Benign	5.3e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.90	N
PhyloP100		1.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.14
Sift	Benign	0.51	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.043
MPC		0.19
ClinPred		0.013	T
GERP RS		4.6
Varity_R		0.028
gMVP		0.20
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1046080; hg19: chr6-31595882;