NM_006813.3:c.11T>C

Variant names:

• chr6-89080905-T-C
• NM_006813.3:c.11T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006813.3(PNRC1):​c.11T>C​(p.Val4Ala) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNRC1 NM_006813.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34

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]

PNRC1-DT (HGNC:55238): (PNRC1 divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNRC1	NM_006813.3	c.11T>C	p.Val4Ala	missense_variant	Exon 1 of 2	ENST00000336032.4	NP_006804.1
PNRC1	XM_047418106.1	c.11T>C	p.Val4Ala	missense_variant	Exon 1 of 2		XP_047274062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNRC1	ENST00000336032.4	c.11T>C	p.Val4Ala	missense_variant	Exon 1 of 2	1	NM_006813.3	ENSP00000336931.3
PNRC1	ENST00000369472	c.-84T>C		5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000358484.1
PNRC1-DT	ENST00000606729.1	n.-238A>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11T>C (p.V4A) alteration is located in exon 1 (coding exon 1) of the PNRC1 gene. This alteration results from a T to C substitution at nucleotide position 11, causing the valine (V) at amino acid position 4 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Benign	0.60
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.89	L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.032
Sift	Benign	0.15	T
Sift4G	Benign	0.39	T
Polyphen		0.0040	B
Vest4		0.13
MutPred		0.48		Loss of sheet (P = 0.0817);
MVP		0.093
MPC		0.72
ClinPred		0.15	T
GERP RS		2.6
Varity_R		0.11
gMVP		0.22

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-89790624;