rs200160678

Variant names:

• chr15-49367517-T-A
• rs200160678
• NM_152647.3:c.1202A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-49367517-T-A
• chr15-49367517-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152647.3(FAM227B):​c.1202A>T​(p.His401Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H401R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM227B NM_152647.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1202A>T	p.His401Leu	missense_variant	Exon 13 of 16	ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1202A>T	p.His401Leu	missense_variant	Exon 13 of 16	2	NM_152647.3	ENSP00000299338.6
GALK2	ENST00000559580.5	c.475T>A	p.Cys159Ser	missense_variant	Exon 4 of 4	5		ENSP00000453257.1
GALK2	ENST00000558399.5	c.452T>A	p.Met151Lys	missense_variant	Exon 4 of 4	5		ENSP00000453252.1
FAM227B	ENST00000559573.3	n.420+3785A>T		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.061	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.52	D
PhyloP100		2.3
PROVEAN	Benign	-0.19	N
Sift	Benign	0.26	T
Sift4G	Benign	0.14	T
MVP		0.87
ClinPred		0.80	D
GERP RS		4.0
Varity_R		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs200160678; hg19: chr15-49659714;