rs547136904

Variant names:

• chr12-4726772-C-G
• rs547136904
• NM_017417.2:c.452C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-4726772-C-G
• chr12-4726772-C-A
• chr12-4726772-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017417.2(GALNT8):​c.452C>G​(p.Ala151Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: GALNT8 NM_017417.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.404
• Publications: 0 publications found

Genes affected

GALNT8 (HGNC:4130): (polypeptide N-acetylgalactosaminyltransferase 8) This gene encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. [provided by RefSeq, Jul 2008]

ENSG00000255639 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14042222).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017417.2. 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
	GALNT8	NM_017417.2	MANE Select	c.452C>G	p.Ala151Gly	missense	Exon 2 of 11	NP_059113.1	Q9NY28

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT8	ENST00000252318.7	TSL:1 MANE Select	c.452C>G	p.Ala151Gly	missense	Exon 2 of 11	ENSP00000252318.2	Q9NY28
	ENSG00000255639	ENST00000648836.1		c.964-34186C>G		intron	N/A	ENSP00000497305.1	A0A3B3ISG8
	GALNT8	ENST00000902363.1		c.452C>G	p.Ala151Gly	missense	Exon 2 of 11	ENSP00000572422.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152034 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000757 AC: 19 AN: 251100 AF XY: 0.0000884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461846 Hom.: 0 Cov.: 33 AF XY: 0.0000481 AC XY: 35 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000510 AC: 44 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111974

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152034 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74260

African (AFR) AF: 0.00 AC: 0 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.40
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.12
Sift	Benign	0.16	T
Sift4G	Benign	0.16	T
Polyphen		0.96	D
Vest4		0.16
MutPred		0.39		Loss of stability (P = 0.0949)
MVP		0.55
MPC		0.18
ClinPred		0.22	T
GERP RS		1.8
Varity_R		0.083
gMVP		0.49
Mutation Taster		=84/16	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: rs547136904; hg19: chr12-4835938;