NM_001131007.2:c.497T>C

Variant names:

• chr4-153557030-T-C
• NM_001131007.2:c.497T>C

Variant summary

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

The NM_001131007.2(TMEM131L):​c.497T>C​(p.Ile166Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM131L NM_001131007.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.48
• Publications: 0 publications found

Genes affected

TMEM131L (HGNC:29146): (transmembrane 131 like) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of immature T cell proliferation in thymus. Located in cytoplasm and plasma 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=0.22726181).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131007.2. 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
	TMEM131L	NM_001131007.2	MANE Select	c.497T>C	p.Ile166Thr	missense	Exon 6 of 35	NP_001124479.1	A2VDJ0-5
	TMEM131L	NM_015196.4		c.497T>C	p.Ile166Thr	missense	Exon 6 of 35	NP_056011.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM131L	ENST00000409959.8	TSL:5 MANE Select	c.497T>C	p.Ile166Thr	missense	Exon 6 of 35	ENSP00000386787.3	A2VDJ0-5
	TMEM131L	ENST00000240487.5	TSL:1	c.80T>C	p.Ile27Thr	missense	Exon 2 of 29	ENSP00000240487.5	H0Y2M0
	TMEM131L	ENST00000409663.7	TSL:5	c.497T>C	p.Ile166Thr	missense	Exon 6 of 35	ENSP00000386574.3	A2VDJ0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

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	Benign	0.12
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.14
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.030	D
Polyphen		0.96	D
Vest4		0.74
MutPred		0.35		Gain of disorder (P = 0.0346)
MVP		0.043
MPC		0.33
ClinPred		0.84	D
GERP RS		5.6
Varity_R		0.13
gMVP		0.51
Mutation Taster		=61/39	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

hg19: chr4-154478182;