chr16-563586-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/19 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

Genes affected

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

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=0.0853287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR35	NM_145270.3	c.292C>T	p.Pro98Ser	missense_variant	Exon 2 of 3	ENST00000409413.4	NP_660313.1
PRR35	XM_017022959.3	c.292C>T	p.Pro98Ser	missense_variant	Exon 2 of 3		XP_016878448.1
PRR35	XM_017022960.3	c.292C>T	p.Pro98Ser	missense_variant	Exon 3 of 4		XP_016878449.1
PRR35	XM_017022961.1	c.170+122C>T		intron_variant	Intron 2 of 3		XP_016878450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR35	ENST00000409413.4	c.292C>T	p.Pro98Ser	missense_variant	Exon 2 of 3	1	NM_145270.3	ENSP00000386499.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.292C>T (p.P98S) alteration is located in exon 2 (coding exon 1) of the PRR35 gene. This alteration results from a C to T substitution at nucleotide position 292, causing the proline (P) at amino acid position 98 to be replaced by a serine (S). 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	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
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

Publications

LitVar

Other links and lift over

dbSNP: rs2035478876; hg19: chr16-613586;