chr9-109046157-C-A

Variant names:

• chr9-109046157-C-A
• rs7041716
• NM_032012.4:c.2123+4126G>T

Variant summary

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

The NM_032012.4(TMEM245):​c.2123+4126G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 511,074 control chromosomes in the GnomAD database, including 4,150 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 0.090 (731 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3419 hom.)
• Consequence: TMEM245 NM_032012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

Genes affected

TMEM245 (HGNC:1363): (transmembrane protein 245) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MIR32 (HGNC:31631): (microRNA 32) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM245	NM_032012.4	c.2123+4126G>T		intron_variant	Intron 14 of 17	ENST00000374586.8	NP_114401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM245	ENST00000374586.8	c.2123+4126G>T		intron_variant	Intron 14 of 17	1	NM_032012.4	ENSP00000363714.3
TMEM245	ENST00000413712.7	c.2099+4126G>T		intron_variant	Intron 13 of 16	2		ENSP00000394798.3
TMEM245	ENST00000491854.1	n.*695+4126G>T		intron_variant	Intron 12 of 15	2		ENSP00000417842.1
MIR32	ENST00000384965.1	n.*72G>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13685 AN: 151940 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0875

GnomAD4 exome AF: 0.126 AC: 45248 AN: 359016 Hom.: 3419 AF XY: 0.135 AC XY: 27549 AN XY: 203510

Gnomad4 AFR exome AF: 0.0375

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.0985

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.0916

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.0901 AC: 13698 AN: 152058 Hom.: 731 Cov.: 32 AF XY: 0.0923 AC XY: 6860 AN XY: 74320

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.0979

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.0856

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0472 Hom.: 51

Bravo AF: 0.0851

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.3
DANN	Benign	0.82

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: rs7041716; hg19: chr9-111808437; COSMIC: COSV63026314; COSMIC: COSV63026314;