6-44275434-C-G

Variant names:

• chr6-44275434-C-G
• rs535594597
• NM_001137560.2:c.608C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001137560.2(TMEM151B):​c.608C>G​(p.Ala203Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,382,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A203V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TMEM151B NM_001137560.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.00
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40019408).

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.608C>G	p.Ala203Gly	missense	Exon 3 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.608C>G	p.Ala203Gly	missense	Exon 3 of 3	ENSP00000393161.2	Q8IW70-1
	ENSG00000272442	ENST00000505802.1	TSL:2	n.312+1928C>G		intron	N/A	ENSP00000424257.1	H0Y9J4
	TMEM151B	ENST00000438774.2	TSL:3	c.576+1928C>G		intron	N/A	ENSP00000409337.2	Q8IW70-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1382944 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 679180

African (AFR) AF: 0.00 AC: 0 AN: 31172

American (AMR) AF: 0.00 AC: 0 AN: 35182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24824

East Asian (EAS) AF: 0.00 AC: 0 AN: 35268

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067868

Other (OTH) AF: 0.00 AC: 0 AN: 57138

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	0.0045	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.57		Gain of catalytic residue at A203 (P = 0.0946)
MVP		0.15
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.60
gMVP		0.76
Mutation Taster		=49/51	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs535594597; hg19: chr6-44243171;