rs2271077

Variant names:

• chr3-16219913-C-T
• rs2271077
• NM_054110.5:c.1528C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054110.5(GALNT15):​c.1528C>T​(p.His510Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 1,612,530 control chromosomes in the GnomAD database, including 6,652 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.091 (791 hom., cov: 33)
  • Exomes 𝑓: 0.074 (5861 hom.)
• Consequence: GALNT15 NM_054110.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020534694).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT15	NM_054110.5	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10	ENST00000339732.10	NP_473451.3
GALNT15	NM_001319051.2	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10		NP_001305980.1
GALNT15	NM_001319052.2	c.118C>T	p.His40Tyr	missense_variant	Exon 3 of 5		NP_001305981.1
GALNT15	XM_005264852.6	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10		XP_005264909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT15	ENST00000339732.10	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10	1	NM_054110.5	ENSP00000344260.5
GALNT15	ENST00000437509.3	c.1528C>T	p.His510Tyr	missense_variant	Exon 8 of 10	1		ENSP00000395873.1
GALNT15	ENST00000489467.1	n.202C>T		non_coding_transcript_exon_variant	Exon 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13789 AN: 152120 Hom.: 794 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.0975 AC: 24508 AN: 251270 AF XY: 0.104

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0485

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.209

Gnomad FIN exome AF: 0.0578

Gnomad NFE exome AF: 0.0610

Gnomad OTH exome AF: 0.0961

GnomAD4 exome AF: 0.0735 AC: 107403 AN: 1460292 Hom.: 5861 Cov.: 31 AF XY: 0.0787 AC XY: 57147 AN XY: 726570

African (AFR) AF: 0.133 AC: 4431 AN: 33420

American (AMR) AF: 0.0512 AC: 2292 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3780 AN: 26118

East Asian (EAS) AF: 0.208 AC: 8260 AN: 39676

South Asian (SAS) AF: 0.214 AC: 18450 AN: 86176

European-Finnish (FIN) AF: 0.0630 AC: 3365 AN: 53420

Middle Eastern (MID) AF: 0.121 AC: 696 AN: 5762

European-Non Finnish (NFE) AF: 0.0545 AC: 60578 AN: 1110662

Other (OTH) AF: 0.0920 AC: 5551 AN: 60336

GnomAD4 genome AF: 0.0906 AC: 13797 AN: 152238 Hom.: 791 Cov.: 33 AF XY: 0.0940 AC XY: 6999 AN XY: 74446

African (AFR) AF: 0.129 AC: 5340 AN: 41532

American (AMR) AF: 0.0659 AC: 1008 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1042 AN: 5174

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4828

European-Finnish (FIN) AF: 0.0598 AC: 635 AN: 10622

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0578 AC: 3928 AN: 68008

Other (OTH) AF: 0.106 AC: 224 AN: 2110

Alfa AF: 0.0747 Hom.: 2380

Bravo AF: 0.0903

TwinsUK AF: 0.0523 AC: 194

ALSPAC AF: 0.0519 AC: 200

ESP6500AA AF: 0.124 AC: 546

ESP6500EA AF: 0.0590 AC: 507

ExAC AF: 0.100 AC: 12165

Asia WGS AF: 0.175 AC: 606 AN: 3478

EpiCase AF: 0.0682

EpiControl AF: 0.0699

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.073
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.77	T;T;T
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.93	L;.;.
PhyloP100		1.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.2	N;N;.
REVEL	Benign	0.026
Sift	Benign	0.21	T;T;.
Sift4G	Benign	0.92	T;T;T
Polyphen		0.010	B;.;.
Vest4		0.078
MPC		0.045
ClinPred		0.0082	T
GERP RS		4.5
Varity_R		0.16
gMVP		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2271077; hg19: chr3-16261420; COSMIC: COSV60215381;