Variant 10-116951926-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001127211.3(SHTN1):c.517G>T(p.Val173Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000819 in 1,587,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

SHTN1
NM_001127211.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

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]

SHTN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12767258).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHTN1	NM_001127211.3 link	c.517G>T	p.Val173Leu	missense_variant	6/17	ENST00000355371.9	NP_001120683.1	A0MZ66-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHTN1	ENST00000355371.9 link	c.517G>T	p.Val173Leu	missense_variant	6/17	2	NM_001127211.3	ENSP00000347532.4		A0MZ66-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247304

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000766

AC:

AN:

1435326

Hom.:

Cov.:

AF XY:

0.00000839

AC XY:

AN XY:

714790

show subpopulations

Gnomad4 AFR exome

AF:

0.0000912

Gnomad4 AMR exome

AF:

0.0000227

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:

9.15e-7

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

Asia WGS

AF:

0.000289

AC:

AN:

3476

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 submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.517G>T (p.V173L) alteration is located in exon 6 (coding exon 6) of the SHTN1 gene. This alteration results from a G to T substitution at nucleotide position 517, causing the valine (V) at amino acid position 173 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

.;.;T;.;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.024

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.84

T;T;T;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.6

L;.;L;L;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.92

.;.;N;N;N

REVEL

Benign

0.050

Sift

Benign

0.28

.;.;T;T;T

Sift4G

Benign

0.47

T;T;T;T;T

Polyphen

0.17

B;.;B;.;.

Vest4

0.31

MutPred

0.11

Loss of ubiquitination at K171 (P = 0.1601);.;Loss of ubiquitination at K171 (P = 0.1601);Loss of ubiquitination at K171 (P = 0.1601);.;

MVP

0.38

MPC

0.49

ClinPred

0.30

GERP RS

5.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.067

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over