chr16-563355-C-T

Variant names:

• chr16-563355-C-T
• NM_145270.3:c.61C>T

Variant summary

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

The NM_145270.3(PRR35):​c.61C>T​(p.Pro21Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRR35 NM_145270.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.61C>T	p.Pro21Ser	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.61C>T	p.Pro21Ser	missense	Exon 2 of 3	ENSP00000386499.3	P0CG20
	PRR35	ENST00000870054.1		c.61C>T	p.Pro21Ser	missense	Exon 2 of 3	ENSP00000540113.1
	PRR35	ENST00000870055.1		c.61C>T	p.Pro21Ser	missense	Exon 3 of 4	ENSP00000540114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459928 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726262

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111668

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome Cov.: 33

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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		6.0
PROVEAN	Pathogenic	-7.7	D
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.37		Gain of phosphorylation at P21 (P = 0.018)
MVP		0.21
MPC		0.56
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.85
gMVP		0.29
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

hg19: chr16-613355;