11-129828961-C-T

Variant names:

• chr11-129828961-C-T
• rs10894147
• NM_138788.5:c.-9+13063C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138788.5(TMEM45B):​c.-9+13063C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,216 control chromosomes in the GnomAD database, including 863 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 (863 hom., cov: 33)
• Consequence: TMEM45B NM_138788.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 18 publications found

Genes affected

TMEM45B (HGNC:25194): (transmembrane protein 45B) Predicted to be integral component of 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138788.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM45B	NM_138788.5	MANE Select	c.-9+13063C>T		intron	N/A	NP_620143.1
	TMEM45B	NM_001331210.2		c.-158-10592C>T		intron	N/A	NP_001318139.1
	TMEM45B	NM_001331211.2		c.-64+13063C>T		intron	N/A	NP_001318140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM45B	ENST00000281441.8	TSL:2 MANE Select	c.-9+13063C>T		intron	N/A	ENSP00000281441.3
	TMEM45B	ENST00000527754.1	TSL:5	n.143+708C>T		intron	N/A
	TMEM45B	ENST00000529381.1	TSL:2	n.28+13063C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15974 AN: 152098 Hom.: 862 Cov.: 33

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0909

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

GnomAD4 genome AF: 0.105 AC: 15986 AN: 152216 Hom.: 863 Cov.: 33 AF XY: 0.105 AC XY: 7794 AN XY: 74420

African (AFR) AF: 0.0832 AC: 3453 AN: 41526

American (AMR) AF: 0.120 AC: 1838 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 328 AN: 3472

East Asian (EAS) AF: 0.111 AC: 575 AN: 5180

South Asian (SAS) AF: 0.104 AC: 503 AN: 4822

European-Finnish (FIN) AF: 0.0991 AC: 1050 AN: 10596

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7937 AN: 68020

Other (OTH) AF: 0.0909 AC: 192 AN: 2112

Alfa AF: 0.112 Hom.: 3057

Bravo AF: 0.106

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.40
PhyloP100		0.071
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: rs10894147; hg19: chr11-129698856;