rs774191878

Variant names:

• chr9-127890658-C-G
• NM_013443.5:c.683G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-127890658-C-G
• chr9-127890658-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013443.5(ST6GALNAC6):​c.683G>C​(p.Arg228Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R228Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST6GALNAC6 NM_013443.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST6GALNAC6	NM_013443.5	c.683G>C	p.Arg228Pro	missense_variant	Exon 5 of 7	ENST00000373146.6	NP_038471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST6GALNAC6	ENST00000373146.6	c.683G>C	p.Arg228Pro	missense_variant	Exon 5 of 7	1	NM_013443.5	ENSP00000362239.1
ENSG00000257524	ENST00000646171.1	n.581G>C		non_coding_transcript_exon_variant	Exon 4 of 13			ENSP00000495484.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460880 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;.;.;.;.;.
Eigen	Benign	-0.062
Eigen_PC	Benign	-0.00041
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;.;D;.;D;.;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.4	M;M;.;.;M;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;D;.;D;D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D;D;.;D;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D;D;D;.
Polyphen		0.44	B;B;B;B;.;B;.
Vest4		0.70
MutPred		0.54		Loss of methylation at R228 (P = 0.0268);Loss of methylation at R228 (P = 0.0268);.;.;Loss of methylation at R228 (P = 0.0268);.;.;
MVP		0.53
MPC		1.5
ClinPred		0.94	D
GERP RS		2.9
Varity_R		0.50
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130652937;