16-563586-C-T

Variant names:

• chr16-563586-C-T
• rs2035478876
• NM_145270.3:c.292C>T

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.292C>T​(p.Pro98Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRR35 NM_145270.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.219
• 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=0.0853287).

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.292C>T	p.Pro98Ser	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.292C>T	p.Pro98Ser	missense	Exon 2 of 3	ENSP00000386499.3	P0CG20
	PRR35	ENST00000870054.1		c.292C>T	p.Pro98Ser	missense	Exon 2 of 3	ENSP00000540113.1
	PRR35	ENST00000870055.1		c.292C>T	p.Pro98Ser	missense	Exon 3 of 4	ENSP00000540114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.079
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.4
DANN	Benign	0.65
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.22
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.065
Sift	Benign	0.36	T
Sift4G	Benign	0.079	T
Polyphen		0.64	P
Vest4		0.14
MutPred		0.14		Gain of phosphorylation at P98 (P = 0.0099)
MVP		0.085
MPC		0.12
ClinPred		0.14	T
GERP RS		3.9
Varity_R		0.031
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2035478876; hg19: chr16-613586;