rs2230279

Variant names:

• chr11-126408180-C-T
• rs2230279
• NM_001254757.2:c.423C>T

Variant summary

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

The NM_001254757.2(ST3GAL4):​c.423C>T​(p.Tyr141Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,613,724 control chromosomes in the GnomAD database, including 78,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7782 hom., cov: 32)
  • Exomes 𝑓: 0.31 (70741 hom.)
• Consequence: ST3GAL4 NM_001254757.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.932
• Publications: 28 publications found

Genes affected

ST3GAL4 (HGNC:10864): (ST3 beta-galactoside alpha-2,3-sialyltransferase 4) This gene encodes a member of the glycosyltransferase 29 family, a group of enzymes involved in protein glycosylation. The encoded protein is targeted to Golgi membranes but may be proteolytically processed and secreted. The gene product may also be involved in the increased expression of sialyl Lewis X antigen seen in inflammatory responses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 11-126408180-C-T is Benign according to our data. Variant chr11-126408180-C-T is described in ClinVar as Benign. ClinVar VariationId is 257674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.932 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001254757.2. 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
	ST3GAL4	NM_001254757.2	MANE Select	c.423C>T	p.Tyr141Tyr	synonymous	Exon 7 of 11	NP_001241686.1
	ST3GAL4	NM_001348396.2		c.486C>T	p.Tyr162Tyr	synonymous	Exon 8 of 12	NP_001335325.1
	ST3GAL4	NM_001348397.2		c.486C>T	p.Tyr162Tyr	synonymous	Exon 8 of 12	NP_001335326.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL4	ENST00000444328.7	TSL:5 MANE Select	c.423C>T	p.Tyr141Tyr	synonymous	Exon 7 of 11	ENSP00000394354.2
	ST3GAL4	ENST00000392669.6	TSL:1	c.423C>T	p.Tyr141Tyr	synonymous	Exon 7 of 11	ENSP00000376437.2
	ST3GAL4	ENST00000526727.5	TSL:1	c.423C>T	p.Tyr141Tyr	synonymous	Exon 6 of 10	ENSP00000436047.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47892 AN: 151904 Hom.: 7779 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.324

GnomAD2 exomes AF: 0.314 AC: 78937 AN: 251328 AF XY: 0.308

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.512

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.308 AC: 450462 AN: 1461702 Hom.: 70741 Cov.: 45 AF XY: 0.305 AC XY: 222088 AN XY: 727138

African (AFR) AF: 0.358 AC: 11994 AN: 33474

American (AMR) AF: 0.332 AC: 14858 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 9493 AN: 26130

East Asian (EAS) AF: 0.469 AC: 18628 AN: 39688

South Asian (SAS) AF: 0.233 AC: 20097 AN: 86246

European-Finnish (FIN) AF: 0.229 AC: 12245 AN: 53416

Middle Eastern (MID) AF: 0.263 AC: 1515 AN: 5768

European-Non Finnish (NFE) AF: 0.308 AC: 342680 AN: 1111874

Other (OTH) AF: 0.314 AC: 18952 AN: 60392

GnomAD4 genome AF: 0.315 AC: 47924 AN: 152022 Hom.: 7782 Cov.: 32 AF XY: 0.311 AC XY: 23139 AN XY: 74284

African (AFR) AF: 0.345 AC: 14307 AN: 41466

American (AMR) AF: 0.322 AC: 4921 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1265 AN: 3472

East Asian (EAS) AF: 0.515 AC: 2653 AN: 5152

South Asian (SAS) AF: 0.231 AC: 1114 AN: 4828

European-Finnish (FIN) AF: 0.221 AC: 2339 AN: 10574

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20298 AN: 67940

Other (OTH) AF: 0.321 AC: 677 AN: 2110

Alfa AF: 0.312 Hom.: 23845

Bravo AF: 0.329

Asia WGS AF: 0.328 AC: 1140 AN: 3478

EpiCase AF: 0.309

EpiControl AF: 0.304

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.1
DANN	Benign	0.72
PhyloP100		-0.93
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: rs2230279; hg19: chr11-126278075; COSMIC: COSV57106561; COSMIC: COSV57106561;