NM_001137560.2:c.38C>A

Variant names:

• chr6-44270780-C-A
• rs966308756
• NM_001137560.2:c.38C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001137560.2(TMEM151B):​c.38C>A​(p.Ala13Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. A13G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM151B NM_001137560.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092674464).

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.38C>A	p.Ala13Asp	missense	Exon 1 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.38C>A	p.Ala13Asp	missense	Exon 1 of 3	ENSP00000393161.2	Q8IW70-1
	TMEM151B	ENST00000438774.2	TSL:3	c.38C>A	p.Ala13Asp	missense	Exon 1 of 3	ENSP00000409337.2	Q8IW70-2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 970030 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 456746

African (AFR) AF: 0.00 AC: 0 AN: 19238

American (AMR) AF: 0.00 AC: 0 AN: 5128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9808

East Asian (EAS) AF: 0.00 AC: 0 AN: 16824

South Asian (SAS) AF: 0.00 AC: 0 AN: 18446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2334

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 847566

Other (OTH) AF: 0.00 AC: 0 AN: 35964

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.93
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.15
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.16
Sift	Benign	0.15	T
Sift4G	Uncertain	0.028	D
Polyphen		0.014	B
Vest4		0.15
MutPred		0.12		Loss of helix (P = 0.0444)
MVP		0.20
ClinPred		0.11	T
GERP RS		1.7
PromoterAI		-0.030	Neutral
Varity_R		0.13
gMVP		0.28
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs966308756; hg19: chr6-44238517;