Genetic Variant NM_030965.3:c.381C>A (chr1-77044323-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.368

Publications

3 publications found

Variant links:

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]

ST6GALNAC5 links:

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ACMG classification

Classification was made for transcript

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

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

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.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0243

AC XY:

17707

AN XY:

727192

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2352

4704

7056

9408

11760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

966

1932

2898

3864

4830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0216

AC:

3294

AN:

152236

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1611

AN XY:

74420

show subpopulations

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:

AN:

5146

South Asian (SAS)

AF:

0.0147

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0502

AC:

532

AN:

10608

Middle Eastern (MID)

AF:

0.0479

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0273

AC:

1859

AN:

68018

Other (OTH)

AF:

0.0227

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

159

318

476

635

794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0130

Hom.:

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

(source)

DANN

Benign

0.77

PhyloP100

0.37

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over