10-116927829-G-C

Variant summary

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

The NM_001127211.3(SHTN1):c.1075C>G(p.Pro359Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SHTN1 NM_001127211.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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]

ACMG classification

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/exons	MANE	UniProt
SHTN1	NM_001127211.3	c.1075C>G	p.Pro359Ala	missense_variant	11/17	ENST00000355371.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHTN1	ENST00000355371.9	c.1075C>G	p.Pro359Ala	missense_variant	11/17	2	NM_001127211.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454600 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723324

Gnomad4 AFR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

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

Jan 24, 2023

The c.1075C>G (p.P359A) alteration is located in exon 11 (coding exon 11) of the SHTN1 gene. This alteration results from a C to G substitution at nucleotide position 1075, causing the proline (P) at amino acid position 359 to be replaced by an alanine (A). 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	0.16
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
Cadd	Pathogenic	26
Dann	Benign	0.97
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.55	D;D;D;D;D
MetaSVM	Uncertain	-0.053	T
MutationAssessor	Benign	1.7	L;.;L;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.66	T
Sift4G	Uncertain	0.025	D;D;D;D;D
Polyphen		1.0	D;.;D;.;.
Vest4		0.57
MutPred		0.23		Loss of glycosylation at P359 (P = 5e-04);.;Loss of glycosylation at P359 (P = 5e-04);Loss of glycosylation at P359 (P = 5e-04);.;
MVP		0.74
MPC		0.94
ClinPred		0.83	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-118687340;