1-77044323-C-T

Variant names:

• chr1-77044323-C-T
• rs35763299
• NM_030965.3:c.381C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_030965.3(ST6GALNAC5):​c.381C>T​(p.Pro127Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,614,004 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (34 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (31 hom.)
• Consequence: ST6GALNAC5 NM_030965.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.368
• Publications: 3 publications found

Genes affected

ST6GALNAC5 (HGNC:19342): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 5) The protein encoded by this gene is a Golgi type II transmembrane glycosyltransferase. The encoded protein catalyzes the transfer of sialic acid to cell surface proteins to modulate cell-cell interactions. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-77044323-C-T is Benign according to our data. Variant chr1-77044323-C-T is described in ClinVar as Benign. ClinVar VariationId is 784950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.368 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1779/152238) while in subpopulation AFR AF = 0.0408 (1694/41558). AF 95% confidence interval is 0.0391. There are 34 homozygotes in GnomAd4. There are 825 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030965.3. 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
	ST6GALNAC5	NM_030965.3	MANE Select	c.381C>T	p.Pro127Pro	synonymous	Exon 3 of 5	NP_112227.1	Q9BVH7
	ST6GALNAC5	NM_001320273.2		c.262-5935C>T		intron	N/A	NP_001307202.1	B4DV27
	ST6GALNAC5	NM_001320274.2		c.262-18652C>T		intron	N/A	NP_001307203.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC5	ENST00000477717.6	TSL:1 MANE Select	c.381C>T	p.Pro127Pro	synonymous	Exon 3 of 5	ENSP00000417583.1	Q9BVH7
	ST6GALNAC5	ENST00000857213.1		c.381C>T	p.Pro127Pro	synonymous	Exon 3 of 4	ENSP00000527272.1
	ST6GALNAC5	ENST00000857212.1		c.262-5939C>T		intron	N/A	ENSP00000527271.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1780 AN: 152120 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00291 AC: 732 AN: 251214 AF XY: 0.00216

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000793

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00111 AC: 1617 AN: 1461766 Hom.: 31 Cov.: 31 AF XY: 0.000972 AC XY: 707 AN XY: 727192

African (AFR) AF: 0.0393 AC: 1315 AN: 33480

American (AMR) AF: 0.00195 AC: 87 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53296

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.0000665 AC: 74 AN: 1112010

Other (OTH) AF: 0.00219 AC: 132 AN: 60396

GnomAD4 genome AF: 0.0117 AC: 1779 AN: 152238 Hom.: 34 Cov.: 32 AF XY: 0.0111 AC XY: 825 AN XY: 74420

African (AFR) AF: 0.0408 AC: 1694 AN: 41558

American (AMR) AF: 0.00386 AC: 59 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68020

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.0135 Hom.: 22

Bravo AF: 0.0133

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	-0.39
CADD	Benign	3.4
DANN	Benign	0.81
PhyloP100		0.37
Mutation Taster		=96/4	polymorphism

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: rs35763299; hg19: chr1-77510008;