rs523340

Positions:

• chr9-109091966-G-A

Variant summary

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

The ENST00000374586.8(TMEM245):​c.917-811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,104 control chromosomes in the GnomAD database, including 921 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 0.10 (921 hom., cov: 33)
• Consequence: TMEM245 ENST00000374586.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM245	NM_032012.4	c.917-811C>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.917-811C>T		intron_variant		1	NM_032012.4	ENSP00000363714	P3
TMEM245	ENST00000413712.7	c.917-811C>T		intron_variant		2		ENSP00000394798	A1
TMEM245	ENST00000491854.1	c.167-811C>T		intron_variant, NMD_transcript_variant		2		ENSP00000417842

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15163 AN: 151986 Hom.: 919 Cov.: 33

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.0976

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.0998 AC: 15178 AN: 152104 Hom.: 921 Cov.: 33 AF XY: 0.101 AC XY: 7542 AN XY: 74336

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.0976

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.0949

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.0975

Alfa AF: 0.121 Hom.: 1908

Bravo AF: 0.0941

Asia WGS AF: 0.168 AC: 584 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.72

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: rs523340; hg19: chr9-111854246;