6-44273106-G-C

Variant names:

• chr6-44273106-G-C
• rs542183426
• NM_001137560.2:c.176G>C

Variant summary

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

The NM_001137560.2(TMEM151B):​c.176G>C​(p.Arg59Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TMEM151B NM_001137560.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM151B	NM_001137560.2	c.176G>C	p.Arg59Pro	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.176G>C	p.Arg59Pro	missense_variant	Exon 2 of 3	5	NM_001137560.2	ENSP00000393161.2
TMEM151B	ENST00000438774.2	c.176G>C	p.Arg59Pro	missense_variant	Exon 2 of 3	3		ENSP00000409337.2
ENSG00000272442	ENST00000505802.1	n.-89G>C		upstream_gene_variant		2		ENSP00000424257.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152172 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74334

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.67
MutPred		0.64		Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);
MVP		0.39
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.91
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs542183426; hg19: chr6-44240843;