6-44270823-G-T

Variant summary

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

The NM_001137560.2(TMEM151B):c.81G>T(p.Glu27Asp) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM151B NM_001137560.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.126

Genes affected

TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

POLR1C (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=0.1523253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM151B	NM_001137560.2	c.81G>T	p.Glu27Asp	missense_variant	1/3	ENST00000451188.7
POLR1C	NM_001318876.2	c.946-171067G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM151B	ENST00000451188.7	c.81G>T	p.Glu27Asp	missense_variant	1/3	5	NM_001137560.2	P1
TMEM151B	ENST00000438774.2	c.81G>T	p.Glu27Asp	missense_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 982328 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 462984

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

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

Apr 07, 2023

The c.81G>T (p.E27D) alteration is located in exon 1 (coding exon 1) of the TMEM151B gene. This alteration results from a G to T substitution at nucleotide position 81, causing the glutamic acid (E) at amino acid position 27 to be replaced by an aspartic acid (D). 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	0.074
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	15
Dann	Benign	0.96
DEOGEN2	Benign	0.0040	T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.0086	N
LIST_S2	Benign	0.38	T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.065
Sift	Benign	0.034	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.93	P;D
Vest4		0.11
MutPred		0.12		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.030
ClinPred		0.20	T
GERP RS		1.5
Varity_R		0.12
gMVP		0.27

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: chr6-44238560;