3-16195760-G-A

Position:

• chr3-16195760-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_054110.5(GALNT15):​c.540G>A​(p.Leu180Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GALNT15 NM_054110.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.003188
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00

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]

GALNT15 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 3-16195760-G-A is Benign according to our data. Variant chr3-16195760-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3098101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT15	NM_054110.5	c.540G>A	p.Leu180Leu	splice_region_variant, synonymous_variant	2/10	ENST00000339732.10	NP_473451.3
GALNT15	NM_001319051.2	c.540G>A	p.Leu180Leu	splice_region_variant, synonymous_variant	2/10		NP_001305980.1
GALNT15	XM_005264852.6	c.540G>A	p.Leu180Leu	splice_region_variant, synonymous_variant	2/10		XP_005264909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT15	ENST00000339732.10	c.540G>A	p.Leu180Leu	splice_region_variant, synonymous_variant	2/10	1	NM_054110.5	ENSP00000344260.5
GALNT15	ENST00000437509.3	c.540G>A	p.Leu180Leu	splice_region_variant, synonymous_variant	2/10	1		ENSP00000395873.1
GALNT15	ENST00000430410.1	n.27G>A		splice_region_variant, non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458052 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724742

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0032
dbscSNV1_RF	Benign	0.18
SpliceAI score (max)		0.020		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: rs2063626420; hg19: chr3-16237267;