rs138996422

Variant names:

• chr6-89081055-C-G
• rs138996422
• NM_006813.3:c.161C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-89081055-C-G
• chr6-89081055-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006813.3(PNRC1):​c.161C>G​(p.Thr54Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,610,580 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (1 hom.)
• Consequence: PNRC1 NM_006813.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.437
• Publications: 0 publications found

Genes affected

PNRC1 (HGNC:17278): (proline rich nuclear receptor coactivator 1) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019788116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006813.3. 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
	PNRC1	NM_006813.3	MANE Select	c.161C>G	p.Thr54Ser	missense	Exon 1 of 2	NP_006804.1	Q12796-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNRC1	ENST00000336032.4	TSL:1 MANE Select	c.161C>G	p.Thr54Ser	missense	Exon 1 of 2	ENSP00000336931.3	Q12796-1
	PNRC1	ENST00000369472.1	TSL:2	c.-16+82C>G		intron	N/A	ENSP00000358484.1	Q49A59

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000471 AC: 116 AN: 246540 AF XY: 0.000470

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000105

Gnomad NFE exome AF: 0.000988

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000367 AC: 535 AN: 1458342 Hom.: 1 Cov.: 34 AF XY: 0.000333 AC XY: 242 AN XY: 725696

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.000378 AC: 19 AN: 50268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000443 AC: 492 AN: 1111702

Other (OTH) AF: 0.000381 AC: 23 AN: 60352

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74368

African (AFR) AF: 0.0000723 AC: 3 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68052

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000201 Hom.: 0

Bravo AF: 0.000261

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.000816 AC: 99

EpiCase AF: 0.000164

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.48	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.44
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.077
Sift	Benign	0.085	T
Sift4G	Benign	0.22	T
Polyphen		0.094	B
Vest4		0.13
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.15
MPC		1.0
ClinPred		0.12	T
GERP RS		3.9
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.12
Mutation Taster		=95/5	polymorphism

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: rs138996422; hg19: chr6-89790774;