9-70536068-C-T

Variant names:

• chr9-70536068-C-T
• rs6560142
• NM_001366145.2:c.5045G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001366145.2(TRPM3):​c.5045G>A​(p.Arg1682Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,613,982 control chromosomes in the GnomAD database, including 261,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1682L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.59 (26643 hom., cov: 32)
  • Exomes 𝑓: 0.56 (235232 hom.)
• Consequence: TRPM3 NM_001366145.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.57
• Publications: 31 publications found

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]

ENSG00000308298 (HGNC:):

KLF9-DT (HGNC:54815): (KLF9 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2846781E-6).
• BP6: Variant 9-70536068-C-T is Benign according to our data. Variant chr9-70536068-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366145.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	NM_001366145.2	MANE Select	c.5045G>A	p.Arg1682Gln	missense	Exon 26 of 26	NP_001353074.1	Q9HCF6-3
	TRPM3	NM_001366147.2		c.5120G>A	p.Arg1707Gln	missense	Exon 27 of 27	NP_001353076.1
	TRPM3	NM_001366141.2		c.5015G>A	p.Arg1672Gln	missense	Exon 25 of 25	NP_001353070.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM3	ENST00000677713.2	MANE Select	c.5045G>A	p.Arg1682Gln	missense	Exon 26 of 26	ENSP00000503830.2	Q9HCF6-3
	TRPM3	ENST00000377110.9	TSL:1	c.5009G>A	p.Arg1670Gln	missense	Exon 25 of 25	ENSP00000366314.4	Q9HCF6-2
	TRPM3	ENST00000377111.8	TSL:1	c.3956-617G>A		intron	N/A	ENSP00000366315.4	Q9HCF6-10

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89386 AN: 151986 Hom.: 26625 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.584

GnomAD2 exomes AF: 0.580 AC: 145754 AN: 251452 AF XY: 0.569

Gnomad AFR exome AF: 0.632

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.563

Gnomad EAS exome AF: 0.841

Gnomad FIN exome AF: 0.655

Gnomad NFE exome AF: 0.570

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.564 AC: 824096 AN: 1461878 Hom.: 235232 Cov.: 84 AF XY: 0.559 AC XY: 406702 AN XY: 727240

African (AFR) AF: 0.646 AC: 21630 AN: 33478

American (AMR) AF: 0.565 AC: 25277 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 14871 AN: 26136

East Asian (EAS) AF: 0.798 AC: 31680 AN: 39700

South Asian (SAS) AF: 0.409 AC: 35284 AN: 86254

European-Finnish (FIN) AF: 0.656 AC: 35034 AN: 53420

Middle Eastern (MID) AF: 0.541 AC: 3118 AN: 5768

European-Non Finnish (NFE) AF: 0.560 AC: 622997 AN: 1112002

Other (OTH) AF: 0.566 AC: 34205 AN: 60396

GnomAD4 genome AF: 0.588 AC: 89440 AN: 152104 Hom.: 26643 Cov.: 32 AF XY: 0.590 AC XY: 43868 AN XY: 74376

African (AFR) AF: 0.630 AC: 26156 AN: 41494

American (AMR) AF: 0.557 AC: 8514 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1991 AN: 3472

East Asian (EAS) AF: 0.821 AC: 4252 AN: 5178

South Asian (SAS) AF: 0.398 AC: 1912 AN: 4810

European-Finnish (FIN) AF: 0.653 AC: 6912 AN: 10580

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37825 AN: 67960

Other (OTH) AF: 0.585 AC: 1236 AN: 2114

Alfa AF: 0.574 Hom.: 90802

Bravo AF: 0.593

TwinsUK AF: 0.561 AC: 2082

ALSPAC AF: 0.565 AC: 2177

ESP6500AA AF: 0.621 AC: 2735

ESP6500EA AF: 0.551 AC: 4741

ExAC AF: 0.579 AC: 70238

Asia WGS AF: 0.580 AC: 2017 AN: 3478

EpiCase AF: 0.565

EpiControl AF: 0.568

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.59
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.99	T
PhyloP100		7.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.23
Sift	Benign	0.045	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.46
MPC		0.58
ClinPred		0.020	T
GERP RS		5.8
gMVP		0.50
Mutation Taster		=98/2	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: rs6560142; hg19: chr9-73150984; COSMIC: COSV62582299;