chr8-10765677-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017884.6(PINX1):​c.711G>C​(p.Glu237Asp) 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. 14/20 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

PINX1
NM_017884.6 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.566
Variant links:
Genes affected
PINX1 (HGNC:30046): (PIN2 (TERF1) interacting telomerase inhibitor 1) Enables telomerase RNA binding activity and telomerase inhibitor activity. Involved in several processes, including negative regulation of DNA biosynthetic process; positive regulation of protein localization to nucleolus; and protein localization to organelle. Acts upstream of or within telomere maintenance via telomerase. Located in several cellular components, including chromosomal region; nuclear lumen; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.12979606).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PINX1NM_017884.6 linkuse as main transcriptc.711G>C p.Glu237Asp missense_variant 7/7 ENST00000314787.8 NP_060354.4
LOC102723313NR_146188.1 linkuse as main transcriptn.341-2723C>G intron_variant, non_coding_transcript_variant
PINX1NM_001284356.2 linkuse as main transcriptc.*109G>C 3_prime_UTR_variant 6/6 NP_001271285.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PINX1ENST00000314787.8 linkuse as main transcriptc.711G>C p.Glu237Asp missense_variant 7/71 NM_017884.6 ENSP00000318966 P2Q96BK5-1
ENST00000657150.1 linkuse as main transcriptn.174-2723C>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 21, 2023The c.711G>C (p.E237D) alteration is located in exon 7 (coding exon 7) of the PINX1 gene. This alteration results from a G to C substitution at nucleotide position 711, causing the glutamic acid (E) at amino acid position 237 to be replaced by an aspartic acid (D). 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
0.090
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
6.3
DANN
Benign
0.94
DEOGEN2
Benign
0.038
T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.045
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
1.0
N;N;N;N
PROVEAN
Benign
-0.050
N
REVEL
Benign
0.074
Sift
Benign
0.053
T
Sift4G
Benign
0.38
T
Polyphen
0.42
B
Vest4
0.15
MutPred
0.10
Loss of loop (P = 0.0112);
MVP
0.47
MPC
0.0017
ClinPred
0.17
T
GERP RS
3.7
Varity_R
0.087
gMVP
0.019

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1801012960; hg19: chr8-10623187; API