rs10517574

Variant names:

• chr4-153589691-G-A
• rs10517574
• NM_001131007.2:c.1670+684G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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: Benign. The variant received -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.

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.1670+684G>A		intron	N/A	NP_001124479.1	A2VDJ0-5
	TMEM131L	NM_015196.4		c.1667+684G>A		intron	N/A	NP_056011.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM131L	ENST00000409959.8	TSL:5 MANE Select	c.1670+684G>A		intron	N/A	ENSP00000386787.3	A2VDJ0-5
	TMEM131L	ENST00000240487.5	TSL:1	c.1253+684G>A		intron	N/A	ENSP00000240487.5	H0Y2M0
	TMEM131L	ENST00000409663.7	TSL:5	c.1667+684G>A		intron	N/A	ENSP00000386574.3	A2VDJ0-1

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

African (AFR) AF: 0.0993 AC: 4125 AN: 41544

American (AMR) AF: 0.200 AC: 3054 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5186

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4826

European-Finnish (FIN) AF: 0.347 AC: 3664 AN: 10552

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.320 AC: 21762 AN: 67968

Other (OTH) AF: 0.262 AC: 554 AN: 2114

Alfa AF: 0.283 Hom.: 12467

Bravo AF: 0.219

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs10517574; hg19: chr4-154510843;