chr6-44273340-G-C

Position:

• chr6-44273340-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001137560.2(TMEM151B):​c.410G>C​(p.Arg137Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM151B NM_001137560.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63

Genes affected

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

ENSG00000272442 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM151B	NM_001137560.2	c.410G>C	p.Arg137Pro	missense_variant	2/3	ENST00000451188.7	NP_001131032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM151B	ENST00000451188.7	c.410G>C	p.Arg137Pro	missense_variant	2/3	5	NM_001137560.2	ENSP00000393161.2
ENSG00000272442	ENST00000505802.1	n.146G>C		non_coding_transcript_exon_variant	1/10	2		ENSP00000424257.1
TMEM151B	ENST00000438774.2	c.410G>C	p.Arg137Pro	missense_variant	2/3	3		ENSP00000409337.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Mar 26, 2024

The c.410G>C (p.R137P) alteration is located in exon 2 (coding exon 2) of the TMEM151B gene. This alteration results from a G to C substitution at nucleotide position 410, causing the arginine (R) at amino acid position 137 to be replaced by a proline (P). 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	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0088	T
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;D
Vest4		0.81
MutPred		0.55		Gain of loop (P = 0.024);Gain of loop (P = 0.024);
MVP		0.37
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.95
gMVP		0.99

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: chr6-44241077;