NM_022479.3:c.497C>T

Variant names:

• chr7-71388309-C-T
• NM_022479.3:c.497C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022479.3(GALNT17):​c.497C>T​(p.Ser166Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GALNT17 NM_022479.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90
• Publications: 0 publications found

Genes affected

GALNT17 (HGNC:16347): (polypeptide N-acetylgalactosaminyltransferase 17) This gene encodes an N-acetylgalactosaminyltransferase. This gene is located centromeric to the common deleted region in Williams-Beuren syndrome (WBS), a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. This protein may play a role in membrane trafficking. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.928

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022479.3. 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
	GALNT17	NM_022479.3	MANE Select	c.497C>T	p.Ser166Leu	missense	Exon 3 of 11	NP_071924.1	Q6IS24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT17	ENST00000333538.10	TSL:1 MANE Select	c.497C>T	p.Ser166Leu	missense	Exon 3 of 11	ENSP00000329654.5	Q6IS24
	GALNT17	ENST00000447516.5	TSL:4	c.431C>T	p.Ser144Leu	missense	Exon 3 of 4	ENSP00000392019.1	H7BZX9
	GALNT17	ENST00000467723.1	TSL:2	n.431C>T		non_coding_transcript_exon	Exon 3 of 11

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.29	D
PhyloP100		7.9
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.81		Loss of catalytic residue at S166 (P = 0.3018)
MVP		0.89
MPC		0.98
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.87
gMVP		0.83
Mutation Taster		=21/79	disease causing

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: chr7-70853295; COSMIC: COSV61157415;