rs1003346

Positions:

• chr9-109053060-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.1855-2368G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,962 control chromosomes in the GnomAD database, including 13,950 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 0.42 (13950 hom., cov: 32)
• Consequence: TMEM245 NM_032012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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 (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM245	NM_032012.4	c.1855-2368G>T		intron_variant		ENST00000374586.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM245	ENST00000374586.8	c.1855-2368G>T		intron_variant		1	NM_032012.4	P3
TMEM245	ENST00000413712.7	c.1831-2368G>T		intron_variant		2		A1
TMEM245	ENST00000491854.1	c.*427-2368G>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64481 AN: 151844 Hom.: 13941 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.425 AC: 64530 AN: 151962 Hom.: 13950 Cov.: 32 AF XY: 0.421 AC XY: 31251 AN XY: 74266

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.415

Alfa AF: 0.420 Hom.: 27549

Bravo AF: 0.425

Asia WGS AF: 0.299 AC: 1040 AN: 3478

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	0.50

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: rs1003346; hg19: chr9-111815340;