4-173009277-A-T

Position:

• chr4-173009277-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034845.3(GALNTL6):​c.1471A>T​(p.Thr491Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • 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: 6.79

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2595476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNTL6	NM_001034845.3	c.1471A>T	p.Thr491Ser	missense_variant	11/13	ENST00000506823.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNTL6	ENST00000506823.6	c.1471A>T	p.Thr491Ser	missense_variant	11/13	1	NM_001034845.3	P1
GALNTL6	ENST00000508122.5	c.1420A>T	p.Thr474Ser	missense_variant	10/12	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459976 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726476

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Apr 04, 2024

The c.1471A>T (p.T491S) alteration is located in exon 11 (coding exon 10) of the GALNTL6 gene. This alteration results from a A to T substitution at nucleotide position 1471, causing the threonine (T) at amino acid position 491 to be replaced by a serine (S). 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	0.095
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.73
DEOGEN2	Benign	0.019	T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.050	N;N;.
REVEL	Benign	0.22
Sift	Benign	0.44	T;T;.
Sift4G	Benign	0.83	T;T;T
Polyphen		0.016	B;.;.
Vest4		0.64
MutPred		0.46		Gain of disorder (P = 0.0359);.;.;
MVP		0.54
MPC		0.46
ClinPred		0.76	D
GERP RS		5.7
Varity_R		0.079
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-173930428;