rs200556221

Variant names:

• chr15-49367562-T-C
• rs200556221
• NM_152647.3:c.1157A>G

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.1157A>G​(p.Asn386Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,604,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: FAM227B NM_152647.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.280
• Publications: 2 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=0.13405287).

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.1157A>G	p.Asn386Ser	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.1157A>G	p.Asn386Ser	missense	Exon 13 of 16	ENSP00000299338.6	Q96M60-1
	FAM227B	ENST00000968444.1		c.914A>G	p.Asn305Ser	missense	Exon 10 of 13	ENSP00000638503.1
	FAM227B	ENST00000968443.1		c.815A>G	p.Asn272Ser	missense	Exon 9 of 12	ENSP00000638502.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000166 AC: 4 AN: 240472 AF XY: 0.00000769

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000128

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1451934 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 722080

African (AFR) AF: 0.00 AC: 0 AN: 32806

American (AMR) AF: 0.0000963 AC: 4 AN: 41558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25872

East Asian (EAS) AF: 0.00 AC: 0 AN: 39370

South Asian (SAS) AF: 0.00 AC: 0 AN: 83480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1109808

Other (OTH) AF: 0.0000500 AC: 3 AN: 59984

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152118 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3472

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	0.079
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.28
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.095
Sift	Benign	0.049	D
Sift4G	Uncertain	0.040	D
Polyphen		0.76	P
Vest4		0.29
MutPred		0.39		Loss of stability (P = 0.1834)
MVP		0.055
MPC		0.042
ClinPred		0.26	T
GERP RS		2.8
Varity_R		0.074
gMVP		0.23
Mutation Taster		=100/0	polymorphism

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: rs200556221; hg19: chr15-49659759;