rs6493364

Variant names:

• chr15-49353213-T-C
• rs6493364
• NM_152647.3:c.1271+14235A>G

Variant summary

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

The NM_152647.3(FAM227B):​c.1271+14235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,078 control chromosomes in the GnomAD database, including 6,398 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6398 hom., cov: 31)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 0 publications found

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

GALK2 (HGNC:4119): (galactokinase 2) This gene encodes a highly efficient N-acetylgalactosamine (GalNAc) kinase, which has galactokinase activity when galactose is present at high concentrations. The encoded protein is a member of the GHMP kinase family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1271+14235A>G		intron_variant	Intron 13 of 15	ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1271+14235A>G		intron_variant	Intron 13 of 15	2	NM_152647.3	ENSP00000299338.6
GALK2	ENST00000559580.5	c.449-14278T>C		intron_variant	Intron 3 of 3	5		ENSP00000453257.1
GALK2	ENST00000558399.5	c.426-14278T>C		intron_variant	Intron 3 of 3	5		ENSP00000453252.1
FAM227B	ENST00000559573.3	n.420+18089A>G		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42240 AN: 151960 Hom.: 6400 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.329

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.278 AC: 42250 AN: 152078 Hom.: 6398 Cov.: 31 AF XY: 0.280 AC XY: 20804 AN XY: 74330

African (AFR) AF: 0.197 AC: 8178 AN: 41522

American (AMR) AF: 0.401 AC: 6119 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 925 AN: 3472

East Asian (EAS) AF: 0.432 AC: 2229 AN: 5154

South Asian (SAS) AF: 0.305 AC: 1468 AN: 4816

European-Finnish (FIN) AF: 0.251 AC: 2645 AN: 10556

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19625 AN: 67976

Other (OTH) AF: 0.327 AC: 690 AN: 2108

Alfa AF: 0.264 Hom.: 683

Bravo AF: 0.289

Asia WGS AF: 0.335 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.71
PhyloP100		0.37
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: rs6493364; hg19: chr15-49645410;