9-127894670-C-A

Variant names:

• chr9-127894670-C-A
• rs779584534
• NM_013443.5:c.139G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013443.5(ST6GALNAC6):​c.139G>T​(p.Val47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V47M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST6GALNAC6 NM_013443.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• Publications: 1 publications found

Genes affected

ST6GALNAC6 (HGNC:23364): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 6) ST6GALNAC6 belongs to a family of sialyltransferases that modify proteins and ceramides on the cell surface to alter cell-cell or cell-extracellular matrix interactions (Tsuchida et al., 2003 [PubMed 12668675]).[supplied by OMIM, Mar 2008]

ENSG00000257524 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111803025).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013443.5. 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
	ST6GALNAC6	NM_013443.5	MANE Select	c.139G>T	p.Val47Leu	missense	Exon 4 of 7	NP_038471.2
	ST6GALNAC6	NM_001286999.2		c.139G>T	p.Val47Leu	missense	Exon 4 of 7	NP_001273928.1	Q969X2-3
	ST6GALNAC6	NM_001400830.1		c.214G>T	p.Val72Leu	missense	Exon 3 of 6	NP_001387759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC6	ENST00000373146.6	TSL:1 MANE Select	c.139G>T	p.Val47Leu	missense	Exon 4 of 7	ENSP00000362239.1	Q969X2-1
	ST6GALNAC6	ENST00000373142.5	TSL:1	c.139G>T	p.Val47Leu	missense	Exon 4 of 7	ENSP00000362235.1	Q969X2-3
	ST6GALNAC6	ENST00000373144.7	TSL:1	c.37G>T	p.Val13Leu	missense	Exon 3 of 6	ENSP00000362237.3	Q969X2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.052
Sift	Benign	0.22	T
Sift4G	Benign	0.35	T
Polyphen		0.035	B
Vest4		0.31
MutPred		0.50		Gain of helix (P = 0.0022)
MVP		0.26
MPC		0.46
ClinPred		0.16	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.40
Mutation Taster		=270/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs779584534; hg19: chr9-130656949;