NM_001127211.3:c.1674-52C>G

Variant names:

• chr10-116886618-G-C
• rs2531685
• NM_001127211.3:c.1674-52C>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.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
• Publications: 9 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]

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

Our verdict: Benign. The variant received -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.

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.1674-52C>G		intron	N/A	NP_001120683.1
	SHTN1	NM_001258298.2		c.1494-52C>G		intron	N/A	NP_001245227.1
	SHTN1	NM_018330.7		c.1360-52C>G		intron	N/A	NP_060800.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHTN1	ENST00000355371.9	TSL:2 MANE Select	c.1674-52C>G		intron	N/A	ENSP00000347532.4
	SHTN1	ENST00000615301.4	TSL:1	c.1360-52C>G		intron	N/A	ENSP00000480109.1
	SHTN1	ENST00000260777.14	TSL:2	c.1494-52C>G		intron	N/A	ENSP00000260777.11

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

GnomAD2 exomes AF: 0.664 AC: 164334 AN: 247508 AF XY: 0.677

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 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

African (AFR) AF: 0.287 AC: 9480 AN: 33046

American (AMR) AF: 0.586 AC: 25793 AN: 43988

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 19583 AN: 25912

East Asian (EAS) AF: 0.493 AC: 19507 AN: 39596

South Asian (SAS) AF: 0.673 AC: 57424 AN: 85386

European-Finnish (FIN) AF: 0.745 AC: 39469 AN: 52978

Middle Eastern (MID) AF: 0.719 AC: 4119 AN: 5726

European-Non Finnish (NFE) AF: 0.747 AC: 827169 AN: 1107470

Other (OTH) AF: 0.690 AC: 41393 AN: 60030

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

African (AFR) AF: 0.292 AC: 12111 AN: 41456

American (AMR) AF: 0.639 AC: 9760 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2613 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2487 AN: 5166

South Asian (SAS) AF: 0.652 AC: 3138 AN: 4812

European-Finnish (FIN) AF: 0.760 AC: 8014 AN: 10550

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50643 AN: 67982

Other (OTH) AF: 0.635 AC: 1339 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.46
PhyloP100		-0.24
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: rs2531685; hg19: chr10-118646129;