chr6-44273247-G-A

Variant names:

• chr6-44273247-G-A
• rs1435928845
• NM_001137560.2:c.317G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001137560.2(TMEM151B):​c.317G>A​(p.Ser106Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 10.0
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137560.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM151B	NM_001137560.2	MANE Select	c.317G>A	p.Ser106Asn	missense	Exon 2 of 3	NP_001131032.1	Q8IW70-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM151B	ENST00000451188.7	TSL:5 MANE Select	c.317G>A	p.Ser106Asn	missense	Exon 2 of 3	ENSP00000393161.2	Q8IW70-1
	ENSG00000272442	ENST00000505802.1	TSL:2	n.53G>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000424257.1	H0Y9J4
	TMEM151B	ENST00000438774.2	TSL:3	c.317G>A	p.Ser106Asn	missense	Exon 2 of 3	ENSP00000409337.2	Q8IW70-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	-0.018	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		10
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.62		Loss of disorder (P = 0.0897)
MVP		0.16
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.65
gMVP		0.96
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1435928845; hg19: chr6-44240984;