16-563613-C-A

Variant names:

• chr16-563613-C-A
• rs779177812
• NM_145270.3:c.319C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145270.3(PRR35):​c.319C>A​(p.Pro107Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,435,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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. P107S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PRR35 NM_145270.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 0 publications found

Genes affected

PRR35 (HGNC:14139): (proline rich 35)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0740076).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145270.3. 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
	PRR35	NM_145270.3	MANE Select	c.319C>A	p.Pro107Thr	missense	Exon 2 of 3	NP_660313.1	P0CG20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR35	ENST00000409413.4	TSL:1 MANE Select	c.319C>A	p.Pro107Thr	missense	Exon 2 of 3	ENSP00000386499.3	P0CG20
	PRR35	ENST00000870054.1		c.319C>A	p.Pro107Thr	missense	Exon 2 of 3	ENSP00000540113.1
	PRR35	ENST00000870055.1		c.319C>A	p.Pro107Thr	missense	Exon 3 of 4	ENSP00000540114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1435906 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 713368

African (AFR) AF: 0.00 AC: 0 AN: 33060

American (AMR) AF: 0.00 AC: 0 AN: 42114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25698

East Asian (EAS) AF: 0.00 AC: 0 AN: 38602

South Asian (SAS) AF: 0.00 AC: 0 AN: 84084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1104302

Other (OTH) AF: 0.00 AC: 0 AN: 59584

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.35
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.16
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.087
Sift	Benign	0.37	T
Sift4G	Benign	0.59	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.12		Gain of phosphorylation at P107 (P = 0.029)
MVP		0.030
MPC		0.18
ClinPred		0.026	T
GERP RS		0.61
Varity_R		0.039
gMVP		0.079

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs779177812; hg19: chr16-613613;