chr9-127896279-G-T

Position:

• chr9-127896279-G-T

Variant summary

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

The NM_013443.5(ST6GALNAC6):​c.80C>A​(p.Pro27His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST6GALNAC6 NM_013443.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29

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]

ST6GALNAC4-ST6GALNAC6-AK1 (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/exons	MANE	Protein	UniProt
ST6GALNAC6	NM_013443.5	c.80C>A	p.Pro27His	missense_variant	3/7	ENST00000373146.6	NP_038471.2
ST6GALNAC4-ST6GALNAC6-AK1	NR_174625.1	n.956C>A		non_coding_transcript_exon_variant	5/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ST6GALNAC6	ENST00000373146.6	c.80C>A	p.Pro27His	missense_variant	3/7	1	NM_013443.5	ENSP00000362239

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.80C>A (p.P27H) alteration is located in exon 3 (coding exon 2) of the ST6GALNAC6 gene. This alteration results from a C to A substitution at nucleotide position 80, causing the proline (P) at amino acid position 27 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N;N
MutationTaster	Benign	1.0	D;D;D;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.15	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.98	D;D;.
Vest4		0.62
MutPred		0.24		Loss of glycosylation at P27 (P = 0.0123);Loss of glycosylation at P27 (P = 0.0123);Loss of glycosylation at P27 (P = 0.0123);
MVP		0.52
MPC		1.5
ClinPred		0.65	D
GERP RS		3.5
Varity_R		0.10
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130658558;