chr9-109046157-C-A

Position:

• chr9-109046157-C-A

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]

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/exons	MANE	Protein	UniProt
TMEM245	NM_032012.4	c.2123+4126G>T		intron_variant		ENST00000374586.8	NP_114401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM245	ENST00000374586.8	c.2123+4126G>T		intron_variant		1	NM_032012.4	ENSP00000363714	P3
TMEM245	ENST00000413712.7	c.2099+4126G>T		intron_variant		2		ENSP00000394798	A1
TMEM245	ENST00000491854.1	c.*695+4126G>T		intron_variant, NMD_transcript_variant		2		ENSP00000417842

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;