rs146070218

Variant names:

• chr14-73251013-C-G
• NM_001365906.3:c.572C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-73251013-C-G
• chr14-73251013-C-T

Variant summary

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

The NM_001365906.3(PAPLN):​c.572C>G​(p.Ala191Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,342 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A191T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PAPLN NM_001365906.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969

Genes affected

PAPLN (HGNC:19262): (papilin, proteoglycan like sulfated glycoprotein) Predicted to enable metalloendopeptidase activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in basement membrane. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.572C>G	p.Ala191Gly	missense_variant	Exon 7 of 27	ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.572C>G	p.Ala191Gly	missense_variant	Exon 7 of 27		NM_001365906.3	ENSP00000495882.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460342 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726508

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;.;T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.59	T;T;.;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.2	.;N;N;N
REVEL	Benign	0.036
Sift	Benign	0.30	.;T;T;T
Sift4G	Benign	0.32	.;T;T;T
Polyphen		0.0020	B;B;B;B
Vest4		0.20, 0.17, 0.18
MutPred		0.51		Loss of stability (P = 0.0758);Loss of stability (P = 0.0758);Loss of stability (P = 0.0758);Loss of stability (P = 0.0758);
MVP		0.19
MPC		0.20
ClinPred		0.089	T
GERP RS		2.5
Varity_R		0.079
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		1.0		Details are displayed if max score is > 0.2
DS_DG_spliceai		1.0		Position offset: -1
DS_DL_spliceai		0.96		Position offset: 17

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: chr14-73717721;