NM_152647.3:c.1405T>A

Variant names:

• chr15-49331794-A-T
• NM_152647.3:c.1405T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152647.3(FAM227B):​c.1405T>A​(p.Phe469Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM227B NM_152647.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25490212).

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.1405T>A	p.Phe469Ile	missense	Exon 15 of 16	NP_689860.2	Q96M60-1
	GALK2	NM_002044.4	MANE Select	c.*3635A>T		3_prime_UTR	Exon 10 of 10	NP_002035.1	Q01415-1
	GALK2	NM_001001556.3		c.*3635A>T		3_prime_UTR	Exon 10 of 10	NP_001001556.1	Q01415-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM227B	ENST00000299338.11	TSL:2 MANE Select	c.1405T>A	p.Phe469Ile	missense	Exon 15 of 16	ENSP00000299338.6	Q96M60-1
	GALK2	ENST00000560031.6	TSL:1 MANE Select	c.*3635A>T		3_prime_UTR	Exon 10 of 10	ENSP00000453129.1	Q01415-1
	GALK2	ENST00000327171.7	TSL:1	c.*3635A>T		3_prime_UTR	Exon 10 of 10	ENSP00000316632.3	Q01415-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.35		Gain of ubiquitination at K468 (P = 0.0737)
MVP		0.076
MPC		0.32
ClinPred		0.75	D
GERP RS		4.5
Varity_R		0.35
gMVP		0.41

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

hg19: chr15-49623991;