6-44273366-G-A

Variant names:

• chr6-44273366-G-A
• NM_001137560.2:c.436G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001137560.2(TMEM151B):​c.436G>A​(p.Val146Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TMEM151B NM_001137560.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2862925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM151B	NM_001137560.2	c.436G>A	p.Val146Met	missense_variant	Exon 2 of 3	ENST00000451188.7	NP_001131032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM151B	ENST00000451188.7	c.436G>A	p.Val146Met	missense_variant	Exon 2 of 3	5	NM_001137560.2	ENSP00000393161.2
ENSG00000272442	ENST00000505802.1	n.172G>A		non_coding_transcript_exon_variant	Exon 1 of 10	2		ENSP00000424257.1
TMEM151B	ENST00000438774.2	c.436G>A	p.Val146Met	missense_variant	Exon 2 of 3	3		ENSP00000409337.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399166 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690106

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: 0.0000126

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

Jun 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.436G>A (p.V146M) alteration is located in exon 2 (coding exon 2) of the TMEM151B gene. This alteration results from a G to A substitution at nucleotide position 436, causing the valine (V) at amino acid position 146 to be replaced by a methionine (M). 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	0.24
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.025	D;D
Sift4G	Uncertain	0.043	D;T
Polyphen		0.98	D;D
Vest4		0.44
MutPred		0.20		Gain of catalytic residue at V146 (P = 0.0344);Gain of catalytic residue at V146 (P = 0.0344);
MVP		0.072
ClinPred		0.82	D
GERP RS		4.7
Varity_R		0.19
gMVP		0.72

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: chr6-44241103;