7-152105247-G-A

Variant names:

• chr7-152105247-G-A
• rs3778922
• NM_022087.4:c.589G>A

Variant summary

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

The NM_022087.4(GALNT11):​c.589G>A​(p.Asp197Asn) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GALNT11 NM_022087.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65
• Publications: 0 publications found

Genes affected

GALNT11 (HGNC:19875): (polypeptide N-acetylgalactosaminyltransferase 11) Enables Notch binding activity and polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via threonine. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000310074 (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=0.18957415).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022087.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT11	NM_022087.4	MANE Select	c.589G>A	p.Asp197Asn	missense splice_region	Exon 5 of 12	NP_071370.2
	GALNT11	NM_001371464.1		c.589G>A	p.Asp197Asn	missense splice_region	Exon 5 of 12	NP_001358393.1
	GALNT11	NM_001371458.1		c.589G>A	p.Asp197Asn	missense splice_region	Exon 6 of 13	NP_001358387.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT11	ENST00000430044.7	TSL:5 MANE Select	c.589G>A	p.Asp197Asn	missense splice_region	Exon 5 of 12	ENSP00000395122.2
	GALNT11	ENST00000434507.6	TSL:2	c.589G>A	p.Asp197Asn	missense splice_region	Exon 7 of 14	ENSP00000416787.1
	GALNT11	ENST00000447778.5	TSL:5	n.*63G>A		splice_region non_coding_transcript_exon	Exon 4 of 7	ENSP00000395078.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.0024
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.57	N
PhyloP100		3.7
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.075
Sift	Benign	0.25	T
Sift4G	Benign	0.38	T
Polyphen		0.17	B
Vest4		0.29
MutPred		0.52		Gain of catalytic residue at D197 (P = 0.0568)
MVP		0.60
MPC		0.79
ClinPred		0.90	D
GERP RS		4.4
Varity_R		0.30
gMVP		0.44
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs3778922; hg19: chr7-151802332;