rs78441178

Variant names:

• chr4-153467211-C-A
• rs78441178
• NM_001131007.2:c.125C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-153467211-C-A
• chr4-153467211-C-T

Variant summary

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

The NM_001131007.2(TMEM131L):​c.125C>A​(p.Ala42Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. A42V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM131L NM_001131007.2 missense, splice_region
• Scores: Splicing: ADA: 0.9053
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 4 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 2 ACMG points.

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

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.125C>A	p.Ala42Glu	missense splice_region	Exon 2 of 35	NP_001124479.1	A2VDJ0-5
	TMEM131L	NM_015196.4		c.125C>A	p.Ala42Glu	missense splice_region	Exon 2 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.125C>A	p.Ala42Glu	missense splice_region	Exon 2 of 35	ENSP00000386787.3	A2VDJ0-5
	TMEM131L	ENST00000409663.7	TSL:5	c.125C>A	p.Ala42Glu	missense splice_region	Exon 2 of 35	ENSP00000386574.3	A2VDJ0-1
	TMEM131L	ENST00000886543.1		c.125C>A	p.Ala42Glu	missense splice_region	Exon 2 of 35	ENSP00000556606.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.36		Gain of solvent accessibility (P = 0.0145)
MVP		0.082
MPC		0.49
ClinPred		0.88	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.61
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.91
dbscSNV1_RF	Benign	0.70
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: rs78441178; hg19: chr4-154388363;