4-173168924-C-A

Variant names:

• chr4-173168924-C-A
• NM_017423.3:c.89C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017423.3(GALNT7):​c.89C>A​(p.Pro30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: GALNT7 NM_017423.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.459
• Publications: 0 publications found

Genes affected

GALNT7 (HGNC:4129): (polypeptide N-acetylgalactosaminyltransferase 7) This gene encodes GalNAc transferase 7, a member of the GalNAc-transferase family. The enzyme encoded by this gene controls the initiation step of mucin-type O-linked protein glycosylation and transfer of N-acetylgalactosamine to serine and threonine amino acid residues. This enzyme is a type II transmembrane protein and shares common sequence motifs with other family members. Unlike other family members, this enzyme shows exclusive specificity for partially GalNAc-glycosylated acceptor substrates and shows no activity with non-glycosylated peptides. This protein may function as a follow-up enzyme in the initiation step of O-glycosylation. [provided by RefSeq, Jul 2008]

GALNT7-DT (HGNC:55604): (GALNT7 divergent transcript)

ENSG00000294732 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15798035).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017423.3. 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
	GALNT7	NM_017423.3	MANE Select	c.89C>A	p.Pro30Gln	missense	Exon 1 of 12	NP_059119.2	Q86SF2
	GALNT7	NM_001375599.1		c.89C>A	p.Pro30Gln	missense	Exon 1 of 12	NP_001362528.1	H0YAH3
	GALNT7	NM_001375600.1		c.89C>A	p.Pro30Gln	missense	Exon 1 of 11	NP_001362529.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT7	ENST00000265000.9	TSL:1 MANE Select	c.89C>A	p.Pro30Gln	missense	Exon 1 of 12	ENSP00000265000.4	Q86SF2
	GALNT7-DT	ENST00000499322.7	TSL:1	n.232G>T		non_coding_transcript_exon	Exon 1 of 4
	GALNT7-DT	ENST00000500914.6	TSL:1	n.729G>T		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

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	0.093
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.46
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.052
Sift	Uncertain	0.022	D
Sift4G	Benign	0.17	T
Polyphen		0.13	B
Vest4		0.20
MutPred		0.18		Loss of glycosylation at P30 (P = 0.0205)
MVP		0.48
MPC		0.78
ClinPred		0.65	D
GERP RS		0.69
PromoterAI		0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.075
gMVP		0.50
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

hg19: chr4-174090075;