12-4745542-A-T

Position:

• chr12-4745542-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017417.2(GALNT8):​c.974A>T​(p.Asp325Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALNT8 NM_017417.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

Genes affected

GALNT8 (HGNC:4130): (polypeptide N-acetylgalactosaminyltransferase 8) This gene encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. [provided by RefSeq, Jul 2008]

ENSG00000255639 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32232094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT8	NM_017417.2	c.974A>T	p.Asp325Val	missense_variant	5/11	ENST00000252318.7	NP_059113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT8	ENST00000252318.7	c.974A>T	p.Asp325Val	missense_variant	5/11	1	NM_017417.2	ENSP00000252318.2
ENSG00000255639	ENST00000648836.1	c.964-15416A>T		intron_variant				ENSP00000497305.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Dec 31, 2023

The c.974A>T (p.D325V) alteration is located in exon 5 (coding exon 5) of the GALNT8 gene. This alteration results from a A to T substitution at nucleotide position 974, causing the aspartic acid (D) at amino acid position 325 to be replaced by a valine (V). 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	0.33
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.26
Sift	Benign	0.41	T
Sift4G	Uncertain	0.031	D
Polyphen		0.75	P
Vest4		0.30
MutPred		0.78		Gain of sheet (P = 0.0477);
MVP		0.47
MPC		0.18
ClinPred		0.69	D
GERP RS		1.8
Varity_R		0.27
gMVP		0.82

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: chr12-4854708;