chr4-153466405-G-T

Variant names:

• chr4-153466405-G-T
• rs745913297
• NM_001131007.2:c.8G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001131007.2(TMEM131L):​c.8G>T​(p.Gly3Val) variant causes a missense change. The variant allele was found at a frequency of 0.000164 in 1,343,502 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G3E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: TMEM131L NM_001131007.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08407706).

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.8G>T	p.Gly3Val	missense	Exon 1 of 35	NP_001124479.1	A2VDJ0-5
	TMEM131L	NM_015196.4		c.8G>T	p.Gly3Val	missense	Exon 1 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.8G>T	p.Gly3Val	missense	Exon 1 of 35	ENSP00000386787.3	A2VDJ0-5
	TMEM131L	ENST00000409663.7	TSL:5	c.8G>T	p.Gly3Val	missense	Exon 1 of 35	ENSP00000386574.3	A2VDJ0-1
	TMEM131L	ENST00000886543.1		c.8G>T	p.Gly3Val	missense	Exon 1 of 35	ENSP00000556606.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 151318 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000962

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000237

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000189 AC: 9 AN: 47718 AF XY: 0.000286

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000329

Gnomad OTH exome AF: 0.00145

GnomAD4 exome AF: 0.000170 AC: 203 AN: 1192184 Hom.: 1 Cov.: 29 AF XY: 0.000172 AC XY: 100 AN XY: 581896

African (AFR) AF: 0.0000402 AC: 1 AN: 24896

American (AMR) AF: 0.000274 AC: 5 AN: 18250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18660

East Asian (EAS) AF: 0.00 AC: 0 AN: 27314

South Asian (SAS) AF: 0.00 AC: 0 AN: 50148

European-Finnish (FIN) AF: 0.000185 AC: 5 AN: 26970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3280

European-Non Finnish (NFE) AF: 0.000191 AC: 186 AN: 974748

Other (OTH) AF: 0.000125 AC: 6 AN: 47918

GnomAD4 genome AF: 0.000112 AC: 17 AN: 151318 Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 4 AN XY: 73886

African (AFR) AF: 0.00 AC: 0 AN: 41350

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000962 AC: 1 AN: 10390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000237 AC: 16 AN: 67612

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000147

ExAC AF: 0.0000652 AC: 1

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	0.31
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0039	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.093
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.075	T
Polyphen		0.98	D
Vest4		0.31
MVP		0.043
MPC		0.57
ClinPred		0.11	T
GERP RS		3.3
PromoterAI		0.19	Neutral
Varity_R		0.28
gMVP		0.49
Mutation Taster		=80/20	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: rs745913297; hg19: chr4-154387557;