10-116948978-T-A

Position:

• chr10-116948978-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001127211.3(SHTN1):​c.554A>T​(p.Glu185Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHTN1 NM_001127211.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31747144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHTN1	NM_001127211.3	c.554A>T	p.Glu185Val	missense_variant	7/17	ENST00000355371.9	NP_001120683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHTN1	ENST00000355371.9	c.554A>T	p.Glu185Val	missense_variant	7/17	2	NM_001127211.3	ENSP00000347532.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.554A>T (p.E185V) alteration is located in exon 7 (coding exon 7) of the SHTN1 gene. This alteration results from a A to T substitution at nucleotide position 554, causing the glutamic acid (E) at amino acid position 185 to be replaced by a valine (V). 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	0.26
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;.;T;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.3	M;.;M;M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.4	.;.;N;N;D
REVEL	Benign	0.15
Sift	Uncertain	0.0030	.;.;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D;D
Polyphen		1.0	D;.;D;.;.
Vest4		0.43
MutPred		0.20		Gain of MoRF binding (P = 0.0198);.;Gain of MoRF binding (P = 0.0198);Gain of MoRF binding (P = 0.0198);.;
MVP		0.58
MPC		1.0
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.23
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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: chr10-118708489;