rs372727242

Variant names:

• chr16-563632-C-A
• rs372727242
• NM_145270.3:c.338C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-563632-C-A
• chr16-563632-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145270.3(PRR35):​c.338C>A​(p.Ala113Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,878 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. A113V) 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: 0.508
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028618455).

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.338C>A	p.Ala113Glu	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.338C>A	p.Ala113Glu	missense	Exon 2 of 3	ENSP00000386499.3	P0CG20
	PRR35	ENST00000870054.1		c.338C>A	p.Ala113Glu	missense	Exon 2 of 3	ENSP00000540113.1
	PRR35	ENST00000870055.1		c.338C>A	p.Ala113Glu	missense	Exon 3 of 4	ENSP00000540114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428878 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 709510

⚠️ 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: 33022

American (AMR) AF: 0.00 AC: 0 AN: 41630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25586

East Asian (EAS) AF: 0.00 AC: 0 AN: 38364

South Asian (SAS) AF: 0.00 AC: 0 AN: 83370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101922

Other (OTH) AF: 0.00 AC: 0 AN: 59384

⚠️ 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
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.19
DANN	Benign	0.40
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.51
PROVEAN	Benign	0.84	N
REVEL	Benign	0.033
Sift	Benign	0.17	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.075
MutPred		0.10		Loss of sheet (P = 7e-04)
MVP		0.055
MPC		0.13
ClinPred		0.20	T
GERP RS		-4.2
Varity_R		0.068
gMVP		0.056

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: rs372727242; hg19: chr16-613632;