rs1905539

Positions:

• chr10-116979803-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127211.3(SHTN1):​c.59-495A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,182 control chromosomes in the GnomAD database, including 4,338 homozygotes. 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: 𝑓 0.24 (4338 hom., cov: 32)
• Consequence: SHTN1 NM_001127211.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHTN1	NM_001127211.3	c.59-495A>G		intron_variant		ENST00000355371.9	NP_001120683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHTN1	ENST00000355371.9	c.59-495A>G		intron_variant		2	NM_001127211.3	ENSP00000347532.4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35888 AN: 152064 Hom.: 4343 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.231

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.236 AC: 35885 AN: 152182 Hom.: 4338 Cov.: 32 AF XY: 0.233 AC XY: 17362 AN XY: 74428

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.231

Alfa AF: 0.233 Hom.: 527

Bravo AF: 0.243

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs1905539; hg19: chr10-118739314;