6-44273484-G-C

Variant names:

• chr6-44273484-G-C
• NM_001137560.2:c.554G>C

Variant summary

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

The NM_001137560.2(TMEM151B):​c.554G>C​(p.Gly185Ala) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 9.77

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, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM151B	NM_001137560.2	c.554G>C	p.Gly185Ala	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.554G>C	p.Gly185Ala	missense_variant	Exon 2 of 3	5	NM_001137560.2	ENSP00000393161.2
ENSG00000272442	ENST00000505802.1	n.290G>C		non_coding_transcript_exon_variant	Exon 1 of 10	2		ENSP00000424257.1
TMEM151B	ENST00000438774.2	c.554G>C	p.Gly185Ala	missense_variant	Exon 2 of 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

Apr 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.554G>C (p.G185A) 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 554, causing the glycine (G) at amino acid position 185 to be replaced by an alanine (A). 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	0.99
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Uncertain	0.022	D
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Pathogenic	0.91
Sift	Uncertain	0.0060	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.98	D;D
Vest4		0.80
MutPred		0.74		Gain of MoRF binding (P = 0.1281);Gain of MoRF binding (P = 0.1281);
MVP		0.15
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.67
gMVP		0.80

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: chr6-44241221;