12-22334002-CG-TT

Variant names:

• chr12-22334002-CG-TT
• NM_003034.4:c.230_231delCGinsAA
• ST8SIA1 p.Ala77Glu

Variant summary

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

The NM_003034.4(ST8SIA1):​c.230_231delCGinsAA​(p.Ala77Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. A77V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST8SIA1 NM_003034.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• Publications: 0 publications found

Genes affected

ST8SIA1 (HGNC:10869): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1) Gangliosides are membrane-bound glycosphingolipids containing sialic acid. Ganglioside GD3 is known to be important for cell adhesion and growth of cultured malignant cells. The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to GM3 to produce gangliosides GD3 and GT3. The encoded protein may be found in the Golgi apparatus and is a member of glycosyltransferase family 29. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2015]

LOC105369151 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003034.4. 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
	ST8SIA1	NM_003034.4	MANE Select	c.230_231delCGinsAA	p.Ala77Glu	missense	N/A	NP_003025.1	Q92185-1
	ST8SIA1	NM_001304450.2		c.-90_-89delCGinsAA		5_prime_UTR	Exon 1 of 4	NP_001291379.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST8SIA1	ENST00000396037.9	TSL:1 MANE Select	c.230_231delCGinsAA	p.Ala77Glu	missense	N/A	ENSP00000379353.3	Q92185-1
	ST8SIA1	ENST00000404299.3	TSL:1	c.230_231delCGinsAA	p.Ala77Glu	missense	N/A	ENSP00000384467.3	F8WCS8
	ST8SIA1	ENST00000381424.3	TSL:1	c.230_231delCGinsAA	p.Ala77Glu	missense	N/A	ENSP00000370832.3	Q86X71

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-22486936;