13-113759280-C-G

Position:

• chr13-113759280-C-G

Variant summary

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

The NM_182614.4(TMEM255B):​c.11C>G​(p.Pro4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000557 in 1,076,700 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: TMEM255B NM_182614.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.458

Genes affected

TMEM255B (HGNC:28297): (transmembrane protein 255B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10124263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM255B	NM_182614.4	c.11C>G	p.Pro4Arg	missense_variant	1/9	ENST00000375353.5
TMEM255B	NM_001348663.2	c.11C>G	p.Pro4Arg	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM255B	ENST00000375353.5	c.11C>G	p.Pro4Arg	missense_variant	1/9	1	NM_182614.4	P1
TMEM255B	ENST00000488362.5	c.11C>G	p.Pro4Arg	missense_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000557 AC: 6 AN: 1076700 Hom.: 0 Cov.: 31 AF XY: 0.00000393 AC XY: 2 AN XY: 508388

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000758

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000436

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.11C>G (p.P4R) alteration is located in exon 1 (coding exon 1) of the TMEM255B gene. This alteration results from a C to G substitution at nucleotide position 11, causing the proline (P) at amino acid position 4 to be replaced by an arginine (R). 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	0.091
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.026	T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.82	D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.52	.;P
Vest4		0.11
MutPred		0.23		Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);
MVP		0.24
MPC		0.072
ClinPred		0.27	T
GERP RS		1.0
Varity_R		0.083
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs1456674889; hg19: chr13-114462253;