15-49367517-T-A

Variant names:

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152647.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	NM_152647.3	MANE Select	c.1202A>T	p.His401Leu	missense	Exon 13 of 16	NP_689860.2	Q96M60-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	ENST00000299338.11	TSL:2 MANE Select	c.1202A>T	p.His401Leu	missense	Exon 13 of 16	ENSP00000299338.6	Q96M60-1
	FAM227B	ENST00000968444.1		c.959A>T	p.His320Leu	missense	Exon 10 of 13	ENSP00000638503.1
	FAM227B	ENST00000968443.1		c.860A>T	p.His287Leu	missense	Exon 9 of 12	ENSP00000638502.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;