9-127890784-G-T

Variant names:

• chr9-127890784-G-T
• rs920599105
• NM_013443.5:c.557C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013443.5(ST6GALNAC6):​c.557C>A​(p.Pro186Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. P186L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ST6GALNAC6 NM_013443.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.68
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38601875).

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.557C>A	p.Pro186Gln	missense	Exon 5 of 7	NP_038471.2
	ST6GALNAC6	NM_001286999.2		c.557C>A	p.Pro186Gln	missense	Exon 5 of 7	NP_001273928.1	Q969X2-3
	ST6GALNAC6	NM_001400830.1		c.632C>A	p.Pro211Gln	missense	Exon 4 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.557C>A	p.Pro186Gln	missense	Exon 5 of 7	ENSP00000362239.1	Q969X2-1
	ST6GALNAC6	ENST00000373142.5	TSL:1	c.557C>A	p.Pro186Gln	missense	Exon 5 of 7	ENSP00000362235.1	Q969X2-3
	ST6GALNAC6	ENST00000373144.7	TSL:1	c.455C>A	p.Pro152Gln	missense	Exon 4 of 6	ENSP00000362237.3	Q969X2-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.096	T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.30	T
Sift4G	Benign	0.60	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.37		Loss of catalytic residue at P185 (P = 0.0096)
MVP		0.58
MPC		1.3
ClinPred		0.92	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.80
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs920599105; hg19: chr9-130653063;