1-76868492-C-T

Position:

• chr1-76868492-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_030965.3(ST6GALNAC5):​c.16-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,599,804 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (92 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (67 hom.)
• Consequence: ST6GALNAC5 NM_030965.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003902
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0290

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

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 1-76868492-C-T is Benign according to our data. Variant chr1-76868492-C-T is described in ClinVar as [Benign]. Clinvar id is 780770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ST6GALNAC5	NM_030965.3	c.16-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000477717.6	NP_112227.1
ST6GALNAC5	NM_001320273.2	c.16-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001307202.1
ST6GALNAC5	NM_001320274.2	c.16-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001307203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST6GALNAC5	ENST00000477717.6	c.16-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_030965.3	ENSP00000417583	P1
ST6GALNAC5	ENST00000318803.6	c.16-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000436263
ST6GALNAC5	ENST00000480428.1	n.212-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		4
ST6GALNAC5	ENST00000496845.1	n.210-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2872 AN: 152184 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00667

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00489 AC: 1172 AN: 239810 Hom.: 27 AF XY: 0.00362 AC XY: 471 AN XY: 130164

Gnomad AFR exome AF: 0.0651

Gnomad AMR exome AF: 0.00365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.00186 AC: 2698 AN: 1447502 Hom.: 67 Cov.: 31 AF XY: 0.00164 AC XY: 1177 AN XY: 718112

Gnomad4 AFR exome AF: 0.0633

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.0000391

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000188

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000142

Gnomad4 OTH exome AF: 0.00426

GnomAD4 genome AF: 0.0190 AC: 2892 AN: 152302 Hom.: 92 Cov.: 32 AF XY: 0.0187 AC XY: 1393 AN XY: 74468

Gnomad4 AFR AF: 0.0658

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0104 Hom.: 16

Bravo AF: 0.0217

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00039
dbscSNV1_RF	Benign	0.022
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

LitVar

Other links and lift over

dbSNP: rs113452830; hg19: chr1-77334177;