4-153558286-C-T

Variant names:

• chr4-153558286-C-T
• rs1481090537
• NM_001131007.2:c.578C>T

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.578C>T​(p.Ser193Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TMEM131L NM_001131007.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• 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=0.14214912).

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.578C>T	p.Ser193Phe	missense	Exon 7 of 35	NP_001124479.1	A2VDJ0-5
	TMEM131L	NM_015196.4		c.578C>T	p.Ser193Phe	missense	Exon 7 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.578C>T	p.Ser193Phe	missense	Exon 7 of 35	ENSP00000386787.3	A2VDJ0-5
	TMEM131L	ENST00000240487.5	TSL:1	c.161C>T	p.Ser54Phe	missense	Exon 3 of 29	ENSP00000240487.5	H0Y2M0
	TMEM131L	ENST00000409663.7	TSL:5	c.578C>T	p.Ser193Phe	missense	Exon 7 of 35	ENSP00000386574.3	A2VDJ0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454978 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 723900

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 85744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106534

Other (OTH) AF: 0.0000333 AC: 2 AN: 60064

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.062
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.5
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.16
Sift	Benign	0.042	D
Sift4G	Uncertain	0.011	D
Polyphen		0.98	D
Vest4		0.28
MutPred		0.39		Loss of disorder (P = 0.0098)
MVP		0.043
MPC		0.42
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.094
gMVP		0.43
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1481090537; hg19: chr4-154479438;