6-44275850-A-G

Variant summary

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

The NM_001137560.2(TMEM151B):c.1024A>G(p.Ser342Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TMEM151B NM_001137560.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.480

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=0.13378927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM151B	NM_001137560.2	c.1024A>G	p.Ser342Gly	missense_variant	3/3	ENST00000451188.7
POLR1C	NM_001318876.2	c.946-166040A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM151B	ENST00000451188.7	c.1024A>G	p.Ser342Gly	missense_variant	3/3	5	NM_001137560.2	P1
TMEM151B	ENST00000438774.2	c.576+2344A>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389760 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 685564

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

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.: 33

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.1024A>G (p.S342G) alteration is located in exon 3 (coding exon 3) of the TMEM151B gene. This alteration results from a A to G substitution at nucleotide position 1024, causing the serine (S) at amino acid position 342 to be replaced by a glycine (G). 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	0.054
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	11
Dann	Benign	0.96
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.28	N
MutationTaster	Benign	1.0	D;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.14
Sift	Benign	0.35	T
Sift4G	Benign	0.52	T
Polyphen		0.95	P
Vest4		0.13
MutPred		0.13		Loss of phosphorylation at S342 (P = 0.0248);
MVP		0.055
ClinPred		0.62	D
GERP RS		3.1
Varity_R		0.099
gMVP		0.53

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: chr6-44243587;