rs643410

Positions:

• chr9-109037283-A-C
• chr9-109037283-A-G
• chr9-109037283-A-T

Variant summary

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

The NM_032012.4(TMEM245):​c.2224+734T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 152,236 control chromosomes in the GnomAD database, including 66,235 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 0.93 (66235 hom., cov: 32)
• Consequence: TMEM245 NM_032012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM245	NM_032012.4	c.2224+734T>G		intron_variant		ENST00000374586.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM245	ENST00000374586.8	c.2224+734T>G		intron_variant		1	NM_032012.4	P3

Frequencies

GnomAD3 genomes AF: 0.932 AC: 141791 AN: 152118 Hom.: 66175 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.939

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

GnomAD4 genome AF: 0.932 AC: 141912 AN: 152236 Hom.: 66235 Cov.: 32 AF XY: 0.933 AC XY: 69437 AN XY: 74422

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.986

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.924

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.939

Alfa AF: 0.942 Hom.: 6717

Bravo AF: 0.930

Asia WGS AF: 0.978 AC: 3401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.80

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: rs643410; hg19: chr9-111799563;