NM_001127211.3:c.1317G>A

Variant names:

• chr10-116911832-C-T
• rs62641722
• NM_001127211.3:c.1317G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001127211.3(SHTN1):​c.1317G>A​(p.Ser439Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,611,472 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (86 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (80 hom.)
• Consequence: SHTN1 NM_001127211.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.144
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 10-116911832-C-T is Benign according to our data. Variant chr10-116911832-C-T is described in ClinVar as Benign. ClinVar VariationId is 768393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.144 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.063 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHTN1	NM_001127211.3	MANE Select	c.1317G>A	p.Ser439Ser	synonymous	Exon 14 of 17	NP_001120683.1	A0MZ66-1
	SHTN1	NM_001258298.2		c.1137G>A	p.Ser379Ser	synonymous	Exon 13 of 16	NP_001245227.1	A0MZ66-5
	SHTN1	NM_001258299.2		c.1317G>A	p.Ser439Ser	synonymous	Exon 14 of 17	NP_001245228.1	A0MZ66-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHTN1	ENST00000355371.9	TSL:2 MANE Select	c.1317G>A	p.Ser439Ser	synonymous	Exon 14 of 17	ENSP00000347532.4	A0MZ66-1
	SHTN1	ENST00000392903.3	TSL:1	c.1317G>A	p.Ser439Ser	synonymous	Exon 14 of 17	ENSP00000376636.3	A0MZ66-4
	SHTN1	ENST00000615301.4	TSL:1	c.1317G>A	p.Ser439Ser	synonymous	Exon 14 of 15	ENSP00000480109.1	A0MZ66-2

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2884 AN: 152110 Hom.: 86 Cov.: 33

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00483 AC: 1213 AN: 250936 AF XY: 0.00349

Gnomad AFR exome AF: 0.0639

Gnomad AMR exome AF: 0.00420

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000794

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00187 AC: 2733 AN: 1459244 Hom.: 80 Cov.: 29 AF XY: 0.00156 AC XY: 1132 AN XY: 726132

African (AFR) AF: 0.0649 AC: 2166 AN: 33376

American (AMR) AF: 0.00501 AC: 224 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000870 AC: 5 AN: 5750

European-Non Finnish (NFE) AF: 0.0000784 AC: 87 AN: 1109780

Other (OTH) AF: 0.00375 AC: 226 AN: 60286

GnomAD4 genome AF: 0.0190 AC: 2885 AN: 152228 Hom.: 86 Cov.: 33 AF XY: 0.0179 AC XY: 1331 AN XY: 74418

African (AFR) AF: 0.0651 AC: 2701 AN: 41512

American (AMR) AF: 0.00921 AC: 141 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68010

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.00906 Hom.: 20

Bravo AF: 0.0213

Asia WGS AF: 0.00231 AC: 8 AN: 3476

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.3
DANN	Benign	0.81
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs62641722; hg19: chr10-118671343;