4-172348587-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001034845.3(GALNTL6):c.451G>C(p.Glu151Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALNTL6 NM_001034845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0

Genes affected

GALNTL6 (HGNC:33844): (polypeptide N-acetylgalactosaminyltransferase like 6) Enables polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via threonine. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNTL6	NM_001034845.3	c.451G>C	p.Glu151Gln	missense_variant	5/13	ENST00000506823.6
GALNTL6	XM_017008244.3	c.475G>C	p.Glu159Gln	missense_variant	4/12
GALNTL6	XM_011531993.3	c.214G>C	p.Glu72Gln	missense_variant	4/12
GALNTL6	XM_017008243.3	c.451G>C	p.Glu151Gln	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNTL6	ENST00000506823.6	c.451G>C	p.Glu151Gln	missense_variant	5/13	1	NM_001034845.3	P1
GALNTL6	ENST00000508122.5	c.400G>C	p.Glu134Gln	missense_variant	4/12	1
GALNTL6	ENST00000457021.1	n.400G>C		non_coding_transcript_exon_variant	3/6	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.451G>C (p.E151Q) alteration is located in exon 5 (coding exon 4) of the GALNTL6 gene. This alteration results from a G to C substitution at nucleotide position 451, causing the glutamic acid (E) at amino acid position 151 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
Cadd	Pathogenic	31
Dann	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.089	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Pathogenic	3.4	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.91
MutPred		0.71		Gain of MoRF binding (P = 0.0648);.;
MVP		0.80
MPC		1.4
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.63
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-173269738;