NM_145270.3:c.445C>A

Variant names:

• chr16-563739-C-A
• rs761819533
• NM_145270.3:c.445C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_145270.3(PRR35):​c.445C>A​(p.Arg149Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,706 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PRR35 NM_145270.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=1.14 with no splicing effect.

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.445C>A	p.Arg149Arg	synonymous	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.445C>A	p.Arg149Arg	synonymous	Exon 2 of 3	ENSP00000386499.3	P0CG20
	PRR35	ENST00000870054.1		c.445C>A	p.Arg149Arg	synonymous	Exon 2 of 3	ENSP00000540113.1
	PRR35	ENST00000870055.1		c.445C>A	p.Arg149Arg	synonymous	Exon 3 of 4	ENSP00000540114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1371706 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 675382

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31366

American (AMR) AF: 0.00 AC: 0 AN: 33624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23428

East Asian (EAS) AF: 0.00 AC: 0 AN: 36194

South Asian (SAS) AF: 0.00 AC: 0 AN: 76710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37586

Middle Eastern (MID) AF: 0.000188 AC: 1 AN: 5310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070604

Other (OTH) AF: 0.00 AC: 0 AN: 56884

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.4
DANN	Benign	0.47
PhyloP100		1.1

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

dbSNP: rs761819533; hg19: chr16-613739;