rs1905539

Variant names:

• chr10-116979803-T-C
• rs1905539
• NM_001127211.3:c.59-495A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127211.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHTN1	NM_001127211.3	MANE Select	c.59-495A>G		intron	N/A	NP_001120683.1
	SHTN1	NM_001258298.2		c.-69-11091A>G		intron	N/A	NP_001245227.1
	SHTN1	NM_001258299.2		c.59-495A>G		intron	N/A	NP_001245228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHTN1	ENST00000355371.9	TSL:2 MANE Select	c.59-495A>G		intron	N/A	ENSP00000347532.4
	SHTN1	ENST00000392903.3	TSL:1	c.59-495A>G		intron	N/A	ENSP00000376636.3
	SHTN1	ENST00000615301.4	TSL:1	c.59-495A>G		intron	N/A	ENSP00000480109.1

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

African (AFR) AF: 0.224 AC: 9294 AN: 41490

American (AMR) AF: 0.257 AC: 3932 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3468

East Asian (EAS) AF: 0.305 AC: 1579 AN: 5174

South Asian (SAS) AF: 0.244 AC: 1177 AN: 4826

European-Finnish (FIN) AF: 0.184 AC: 1954 AN: 10606

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.241 AC: 16384 AN: 68006

Other (OTH) AF: 0.231 AC: 488 AN: 2116

Alfa AF: 0.233 Hom.: 548

Bravo AF: 0.243

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.30
PhyloP100		-0.081
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1905539; hg19: chr10-118739314;