chr3-16175298-C-A

Position:

• chr3-16175298-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_054110.5(GALNT15):​c.147C>A​(p.Ser49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)
• Consequence: GALNT15 NM_054110.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.199

Genes affected

GALNT15 (HGNC:21531): (polypeptide N-acetylgalactosaminyltransferase 15) Predicted to enable polypeptide N-acetylgalactosaminyltransferase activity. Predicted to be involved in O-glycan processing. Located in transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058186233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT15	NM_054110.5	c.147C>A	p.Ser49Arg	missense_variant	1/10	ENST00000339732.10	NP_473451.3
GALNT15	NM_001319051.2	c.147C>A	p.Ser49Arg	missense_variant	1/10		NP_001305980.1
GALNT15	XM_005264852.6	c.147C>A	p.Ser49Arg	missense_variant	1/10		XP_005264909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT15	ENST00000339732.10	c.147C>A	p.Ser49Arg	missense_variant	1/10	1	NM_054110.5	ENSP00000344260.5
GALNT15	ENST00000437509.3	c.147C>A	p.Ser49Arg	missense_variant	1/10	1		ENSP00000395873.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Jan 23, 2024

The c.147C>A (p.S49R) alteration is located in exon 1 (coding exon 1) of the GALNT15 gene. This alteration results from a C to A substitution at nucleotide position 147, causing the serine (S) at amino acid position 49 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0071	T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.018
Sift	Benign	0.037	D;D
Sift4G	Benign	0.081	T;T
Polyphen		0.089	B;.
Vest4		0.17
MutPred		0.23		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.18
MPC		0.057
ClinPred		0.059	T
GERP RS		1.9
Varity_R		0.090
gMVP		0.43

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: chr3-16216805;