chr9-71266013-T-G

Variant names:

• chr9-71266013-T-G
• rs10781006
• ENST00000354500.6:n.252+180640A>C

Variant summary

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

The NM_001366141.2(TRPM3):​c.183+180640A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 152,282 control chromosomes in the GnomAD database, including 72,017 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 0.97 (72017 hom., cov: 32)
• Consequence: TRPM3 NM_001366141.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

Genes affected

TRPM3 (HGNC:17992): (transient receptor potential cation channel subfamily M member 3) The product of this gene belongs to the family of transient receptor potential (TRP) channels. TRP channels are cation-selective channels important for cellular calcium signaling and homeostasis. The protein encoded by this gene mediates calcium entry, and this entry is potentiated by calcium store depletion. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM3	NM_001366141.2	c.183+180640A>C		intron_variant	Intron 1 of 24		NP_001353070.1
TRPM3	NM_001366142.2	c.183+180640A>C		intron_variant	Intron 1 of 26		NP_001353071.1
TRPM3	NM_001366143.2	c.183+180640A>C		intron_variant	Intron 1 of 25		NP_001353072.1
TRPM3	NM_001366144.2	c.183+180640A>C		intron_variant	Intron 1 of 6		NP_001353073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM3	ENST00000354500.6	n.252+180640A>C		intron_variant	Intron 1 of 5	1
TRPM3	ENST00000357533.6	c.183+180640A>C		intron_variant	Intron 1 of 24	5		ENSP00000350140.2

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147900 AN: 152164 Hom.: 71963 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.978

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

GnomAD4 genome AF: 0.972 AC: 148013 AN: 152282 Hom.: 72017 Cov.: 32 AF XY: 0.973 AC XY: 72453 AN XY: 74440

Gnomad4 AFR AF: 0.919

Gnomad4 AMR AF: 0.983

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.993

Gnomad4 OTH AF: 0.978

Alfa AF: 0.976 Hom.: 9706

Bravo AF: 0.967

Asia WGS AF: 0.995 AC: 3461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10781006; hg19: chr9-73880929;