NM_030965.3:c.251C>T

Variant names:

• chr1-76868732-C-T
• rs1021398071
• NM_030965.3:c.251C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030965.3(ST6GALNAC5):​c.251C>T​(p.Ala84Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000442 in 1,356,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: ST6GALNAC5 NM_030965.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.453
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05203539).

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.251C>T	p.Ala84Val	missense	Exon 2 of 5	NP_112227.1	Q9BVH7
	ST6GALNAC5	NM_001320273.2		c.251C>T	p.Ala84Val	missense	Exon 2 of 4	NP_001307202.1	B4DV27
	ST6GALNAC5	NM_001320274.2		c.251C>T	p.Ala84Val	missense	Exon 2 of 3	NP_001307203.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC5	ENST00000477717.6	TSL:1 MANE Select	c.251C>T	p.Ala84Val	missense	Exon 2 of 5	ENSP00000417583.1	Q9BVH7
	ST6GALNAC5	ENST00000857213.1		c.251C>T	p.Ala84Val	missense	Exon 2 of 4	ENSP00000527272.1
	ST6GALNAC5	ENST00000857212.1		c.251C>T	p.Ala84Val	missense	Exon 2 of 4	ENSP00000527271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000442 AC: 6 AN: 1356880 Hom.: 0 Cov.: 31 AF XY: 0.00000300 AC XY: 2 AN XY: 667118

African (AFR) AF: 0.00 AC: 0 AN: 29780

American (AMR) AF: 0.00 AC: 0 AN: 28430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22294

East Asian (EAS) AF: 0.00 AC: 0 AN: 34830

South Asian (SAS) AF: 0.00 AC: 0 AN: 72134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5514

European-Non Finnish (NFE) AF: 0.00000564 AC: 6 AN: 1063606

Other (OTH) AF: 0.00 AC: 0 AN: 56242

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.4	N
PhyloP100		0.45
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.028
Sift	Benign	0.51	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.40		Loss of ubiquitination at K87 (P = 0.0573)
MVP		0.043
MPC		0.34
ClinPred		0.26	T
GERP RS		0.26
Varity_R		0.036
gMVP		0.17
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1021398071; hg19: chr1-77334417;