10-116906651-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001127211.3(SHTN1):​c.1456G>A​(p.Val486Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,016 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V486L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SHTN1
NM_001127211.3 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.782
Variant links:
Genes affected
SHTN1 (HGNC:29319): (shootin 1) Enables identical protein binding activity. Involved in positive regulation of neuron migration. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
ENO4 (HGNC:31670): (enolase 4) Predicted to enable phosphopyruvate hydratase activity. Predicted to be involved in glycolytic process and regulation of vacuole fusion, non-autophagic. Predicted to act upstream of or within cilium organization and flagellated sperm motility. Predicted to be located in sperm principal piece. Predicted to be part of phosphopyruvate hydratase complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SHTN1NM_001127211.3 linkc.1456G>A p.Val486Met missense_variant Exon 15 of 17 ENST00000355371.9 NP_001120683.1 A0MZ66-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SHTN1ENST00000355371.9 linkc.1456G>A p.Val486Met missense_variant Exon 15 of 17 2 NM_001127211.3 ENSP00000347532.4 A0MZ66-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461016
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726798
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
.;T;.;.
Eigen
Benign
-0.098
Eigen_PC
Benign
-0.031
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.92
D;D;D;D
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.6
.;L;L;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.5
N;N;N;N
REVEL
Benign
0.048
Sift
Uncertain
0.0030
D;T;T;T
Sift4G
Uncertain
0.035
D;T;D;D
Polyphen
0.50
.;P;.;.
Vest4
0.29
MutPred
0.15
.;Loss of methylation at K485 (P = 0.0191);Loss of methylation at K485 (P = 0.0191);.;
MVP
0.068
MPC
0.54
ClinPred
0.73
D
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.038
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.22
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.22
Position offset: -24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-118666162; API