rs1003346

Variant names:

• chr9-109053060-C-A
• rs1003346
• NM_032012.4:c.1855-2368G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMEM245	NM_032012.4	c.1855-2368G>T		intron_variant	Intron 12 of 17	ENST00000374586.8	NP_114401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM245	ENST00000374586.8	c.1855-2368G>T		intron_variant	Intron 12 of 17	1	NM_032012.4	ENSP00000363714.3
TMEM245	ENST00000413712.7	c.1831-2368G>T		intron_variant	Intron 11 of 16	2		ENSP00000394798.3
TMEM245	ENST00000491854.1	n.*427-2368G>T		intron_variant	Intron 10 of 15	2		ENSP00000417842.1

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

African (AFR) AF: 0.463 AC: 19177 AN: 41448

American (AMR) AF: 0.424 AC: 6474 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1555 AN: 3472

East Asian (EAS) AF: 0.283 AC: 1466 AN: 5178

South Asian (SAS) AF: 0.309 AC: 1487 AN: 4812

European-Finnish (FIN) AF: 0.430 AC: 4536 AN: 10542

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28573 AN: 67938

Other (OTH) AF: 0.415 AC: 874 AN: 2104

Alfa AF: 0.422 Hom.: 43300

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
PhyloP100		-0.031
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: rs1003346; hg19: chr9-111815340;