chr6-166307523-G-T

Variant names:

• chr6-166307523-G-T
• rs749679057
• NM_175922.4:c.620C>A

Variant summary

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

The NM_175922.4(PRR18):​c.620C>A​(p.Ala207Glu) 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. 15/22 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. A207T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRR18 NM_175922.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 0 publications found

Genes affected

PRR18 (HGNC:28574): (proline rich 18)

LOC107986669 (HGNC:):

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=0.032527238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR18	NM_175922.4	c.620C>A	p.Ala207Glu	missense_variant	Exon 1 of 1	ENST00000322583.5	NP_787118.2
LOC107986669	XR_001744464.2	n.-25G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR18	ENST00000322583.5	c.620C>A	p.Ala207Glu	missense_variant	Exon 1 of 1	6	NM_175922.4	ENSP00000319590.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1080932 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 513586

African (AFR) AF: 0.00 AC: 0 AN: 22374

American (AMR) AF: 0.00 AC: 0 AN: 7822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13656

East Asian (EAS) AF: 0.00 AC: 0 AN: 25214

South Asian (SAS) AF: 0.00 AC: 0 AN: 23222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2980

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920994

Other (OTH) AF: 0.00 AC: 0 AN: 42942

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.7
DANN	Benign	0.37
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.0070
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.025
Sift	Benign	0.50	T
Sift4G	Benign	0.16	T
Polyphen		0.051	B
Vest4		0.042
MutPred		0.21		Gain of solvent accessibility (P = 0.0068);
MVP		0.014
MPC		1.1
ClinPred		0.063	T
GERP RS		0.17
Varity_R		0.061
gMVP		0.065
Mutation Taster		=100/0	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

dbSNP: rs749679057; hg19: chr6-166721011;