10-116886618-G-C

Position:

• chr10-116886618-G-C

Variant summary

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

The NM_001127211.3(SHTN1):​c.1674-52C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,606,144 control chromosomes in the GnomAD database, including 410,744 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 0.60 (30278 hom., cov: 32)
  • Exomes 𝑓: 0.72 (380466 hom.)
• Consequence: SHTN1 NM_001127211.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

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]

ENO4 (HGNC:31670): (enolase 4) Predicted to enable phosphopyruvate hydratase activity. Predicted to be involved in glycolytic process and regulation of vacuole fusion, non-autophagic. Predicted to act upstream of or within cilium organization and flagellated sperm motility. Predicted to be located in sperm principal piece. Predicted to be part of phosphopyruvate hydratase complex. [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 (NFE) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHTN1	NM_001127211.3	c.1674-52C>G		intron_variant		ENST00000355371.9	NP_001120683.1
SHTN1	NM_001258298.2	c.1494-52C>G		intron_variant			NP_001245227.1
SHTN1	NM_018330.7	c.1360-52C>G		intron_variant			NP_060800.2
ENO4	XM_006717835.4	c.1723+6632G>C		intron_variant			XP_006717898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHTN1	ENST00000355371.9	c.1674-52C>G		intron_variant		2	NM_001127211.3	ENSP00000347532	P1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91011 AN: 151892 Hom.: 30271 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.636

GnomAD3 exomes AF: 0.664 AC: 164334 AN: 247508 Hom.: 56646 AF XY: 0.677 AC XY: 90701 AN XY: 133912

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.582

Gnomad ASJ exome AF: 0.754

Gnomad EAS exome AF: 0.479

Gnomad SAS exome AF: 0.676

Gnomad FIN exome AF: 0.748

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.700

GnomAD4 exome AF: 0.718 AC: 1043937 AN: 1454132 Hom.: 380466 Cov.: 34 AF XY: 0.719 AC XY: 519533 AN XY: 722788

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.756

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.745

Gnomad4 NFE exome AF: 0.747

Gnomad4 OTH exome AF: 0.690

GnomAD4 genome AF: 0.599 AC: 91038 AN: 152012 Hom.: 30278 Cov.: 32 AF XY: 0.602 AC XY: 44731 AN XY: 74280

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.635

Alfa AF: 0.684 Hom.: 6732

Bravo AF: 0.573

Asia WGS AF: 0.537 AC: 1868 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	4.0
DANN	Benign	0.46

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: rs2531685; hg19: chr10-118646129;