rs10520549

Positions:

• chr2-97883349-A-G

Variant summary

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

The NM_015348.2(TMEM131):​c.359+4703T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,108 control chromosomes in the GnomAD database, including 1,326 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 0.11 (1326 hom., cov: 32)
• Consequence: TMEM131 NM_015348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

Genes affected

TMEM131 (HGNC:30366): (transmembrane protein 131) Predicted to be integral component of membrane. Predicted to be active in 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM131	NM_015348.2	c.359+4703T>C		intron_variant		ENST00000186436.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM131	ENST00000186436.10	c.359+4703T>C		intron_variant		5	NM_015348.2	P1
TMEM131	ENST00000438715.1	c.20+4703T>C		intron_variant		4
TMEM131	ENST00000418629.6	c.241+4703T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16316 AN: 151990 Hom.: 1326 Cov.: 32

Gnomad AFR AF: 0.0252

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.0737

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

GnomAD4 genome AF: 0.107 AC: 16316 AN: 152108 Hom.: 1326 Cov.: 32 AF XY: 0.109 AC XY: 8119 AN XY: 74348

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.0730

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.134 Hom.: 1939

Bravo AF: 0.0900

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.37

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: rs10520549; hg19: chr2-98499812;