14-69333126-C-G

Position:

• chr14-69333126-C-G

Variant summary

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

The NM_001168368.2(GALNT16):​c.820C>G​(p.Leu274Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GALNT16 NM_001168368.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.74

Genes affected

GALNT16 (HGNC:23233): (polypeptide N-acetylgalactosaminyltransferase 16) Enables polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via serine and 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=0.18708718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT16	NM_001168368.2	c.820C>G	p.Leu274Val	missense_variant	8/15	ENST00000448469.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT16	ENST00000448469.8	c.820C>G	p.Leu274Val	missense_variant	8/15	1	NM_001168368.2	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Jan 16, 2024

The c.820C>G (p.L274V) alteration is located in exon 8 (coding exon 8) of the GALNT16 gene. This alteration results from a C to G substitution at nucleotide position 820, causing the leucine (L) at amino acid position 274 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	0.082
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.011	T;T;.
Eigen	Benign	0.057
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L;L;L
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.26	N;N;N
REVEL	Benign	0.089
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.063	B;B;.
Vest4		0.17
MutPred		0.40		Gain of catalytic residue at L274 (P = 0.007);Gain of catalytic residue at L274 (P = 0.007);Gain of catalytic residue at L274 (P = 0.007);
MVP		0.58
MPC		0.48
ClinPred		0.84	D
GERP RS		4.9
Varity_R		0.19
gMVP		0.28

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: chr14-69799843;