chr12-63779976-A-G

Position:

• chr12-63779976-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014254.3(RXYLT1):​c.16A>G​(p.Lys6Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K6R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RXYLT1 NM_014254.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

Genes affected

RXYLT1 (HGNC:13530): (ribitol xylosyltransferase 1) This gene encodes a type II transmembrane protein that is thought to have glycosyltransferase function. Mutations in this gene result in cobblestone lissencephaly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

ENSG00000249753 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20595402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXYLT1	NM_014254.3	c.16A>G	p.Lys6Glu	missense_variant	1/6	ENST00000261234.11	NP_055069.1
RXYLT1	XM_047428079.1	c.16A>G	p.Lys6Glu	missense_variant	1/5		XP_047284035.1
RXYLT1	NM_001278237.2	c.-1098A>G		5_prime_UTR_variant	1/6		NP_001265166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXYLT1	ENST00000261234.11	c.16A>G	p.Lys6Glu	missense_variant	1/6	1	NM_014254.3	ENSP00000261234.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.16A>G (p.K6E) alteration is located in exon 1 (coding exon 1) of the TMEM5 gene. This alteration results from a A to G substitution at nucleotide position 16, causing the lysine (K) at amino acid position 6 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.085
Eigen_PC	Benign	-0.087
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.035
Sift	Uncertain	0.021	D
Sift4G	Benign	0.064	T
Polyphen		0.59	P
Vest4		0.40
MutPred		0.33		Loss of MoRF binding (P = 1e-04);
MVP		0.072
MPC		1.9
ClinPred		0.80	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.26
gMVP		0.60

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-64173756;