1-77044323-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_030965.3(ST6GALNAC5):​c.381C>A​(p.Pro127Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,614,002 control chromosomes in the GnomAD database, including 631 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. Synonymous variant affecting the same amino acid position (i.e. P127P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.022 (60 hom., cov: 32)
  • Exomes 𝑓: 0.024 (571 hom.)
• Consequence: ST6GALNAC5 NM_030965.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.368 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

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>A	p.Pro127Pro	synonymous	Exon 3 of 5	NP_112227.1	Q9BVH7
	ST6GALNAC5	NM_001320273.2		c.262-5935C>A		intron	N/A	NP_001307202.1	B4DV27
	ST6GALNAC5	NM_001320274.2		c.262-18652C>A		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>A	p.Pro127Pro	synonymous	Exon 3 of 5	ENSP00000417583.1	Q9BVH7
	ST6GALNAC5	ENST00000857213.1		c.381C>A	p.Pro127Pro	synonymous	Exon 3 of 4	ENSP00000527272.1
	ST6GALNAC5	ENST00000857212.1		c.262-5939C>A		intron	N/A	ENSP00000527271.1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3293 AN: 152118 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.00343

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.0252 AC: 6335 AN: 251214 AF XY: 0.0264

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.0166

Gnomad ASJ exome AF: 0.0821

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0448

Gnomad NFE exome AF: 0.0281

Gnomad OTH exome AF: 0.0334

GnomAD4 exome AF: 0.0242 AC: 35405 AN: 1461766 Hom.: 571 Cov.: 31 AF XY: 0.0243 AC XY: 17707 AN XY: 727192

African (AFR) AF: 0.00427 AC: 143 AN: 33480

American (AMR) AF: 0.0177 AC: 790 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0849 AC: 2219 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0174 AC: 1499 AN: 86258

European-Finnish (FIN) AF: 0.0416 AC: 2218 AN: 53296

Middle Eastern (MID) AF: 0.0583 AC: 336 AN: 5766

European-Non Finnish (NFE) AF: 0.0240 AC: 26699 AN: 1112010

Other (OTH) AF: 0.0248 AC: 1498 AN: 60396

GnomAD4 genome AF: 0.0216 AC: 3294 AN: 152236 Hom.: 60 Cov.: 32 AF XY: 0.0216 AC XY: 1611 AN XY: 74420

African (AFR) AF: 0.00342 AC: 142 AN: 41558

American (AMR) AF: 0.0239 AC: 365 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3472

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

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4824

European-Finnish (FIN) AF: 0.0502 AC: 532 AN: 10608

Middle Eastern (MID) AF: 0.0479 AC: 14 AN: 292

European-Non Finnish (NFE) AF: 0.0273 AC: 1859 AN: 68018

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0130 Hom.: 22

Bravo AF: 0.0194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.9
DANN	Benign	0.77
PhyloP100		0.37
Mutation Taster		=96/4	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: rs35763299; hg19: chr1-77510008; COSMIC: COSV59561627;