4-173039994-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001034845.3(GALNTL6):c.1700A>T(p.Lys567Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GALNTL6 NM_001034845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNTL6	NM_001034845.3	c.1700A>T	p.Lys567Met	missense_variant	13/13	ENST00000506823.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNTL6	ENST00000506823.6	c.1700A>T	p.Lys567Met	missense_variant	13/13	1	NM_001034845.3	P1
GALNTL6	ENST00000508122.5	c.1649A>T	p.Lys550Met	missense_variant	12/12	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461564 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

Nov 08, 2021

The c.1700A>T (p.K567M) alteration is located in exon 13 (coding exon 12) of the GALNTL6 gene. This alteration results from a A to T substitution at nucleotide position 1700, causing the lysine (K) at amino acid position 567 to be replaced by a methionine (M). 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	Benign	0.24
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Benign	0.21
Sift	Uncertain	0.0080	D;D;.
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.98	D;.;.
Vest4		0.39
MutPred		0.52		Loss of ubiquitination at K567 (P = 0.0183);.;.;
MVP		0.51
MPC		1.6
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.18
gMVP		0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1753840928; hg19: chr4-173961145;