rs10517574

chr4-153589691-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001131007.2(TMEM131L):c.1670+684G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,148 control chromosomes in the GnomAD database, including 5,060 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5060 hom., cov: 32)
• Consequence: TMEM131L NM_001131007.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM131L	NM_001131007.2	c.1670+684G>A		intron_variant		ENST00000409959.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM131L	ENST00000409959.8	c.1670+684G>A		intron_variant		5	NM_001131007.2	A2
TMEM131L	ENST00000240487.5	c.1253+684G>A		intron_variant		1
TMEM131L	ENST00000409663.7	c.1667+684G>A		intron_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36457 AN: 152030 Hom.: 5054 Cov.: 32

Gnomad AFR AF: 0.0994

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.257

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.240 AC: 36470 AN: 152148 Hom.: 5060 Cov.: 32 AF XY: 0.239 AC XY: 17789 AN XY: 74380

Gnomad4 AFR AF: 0.0993

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.262

Alfa AF: 0.292 Hom.: 9544

Bravo AF: 0.219

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.4
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs10517574; hg19: chr4-154510843;