9-70536388-C-T

Variant names:

• chr9-70536388-C-T
• rs138910787
• NM_001366145.2:c.4725G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001366145.2(TRPM3):​c.4725G>A​(p.Ala1575Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: TRPM3 NM_001366145.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.097).
• BP6: Variant 9-70536388-C-T is Benign according to our data. Variant chr9-70536388-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3770889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BS2: High AC in GnomAd4 at 72 AD,Unknown gene.

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.4725G>A	p.Ala1575Ala	synonymous	Exon 26 of 26	NP_001353074.1	Q9HCF6-3
	TRPM3	NM_001366147.2		c.4800G>A	p.Ala1600Ala	synonymous	Exon 27 of 27	NP_001353076.1
	TRPM3	NM_001366141.2		c.4695G>A	p.Ala1565Ala	synonymous	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.4725G>A	p.Ala1575Ala	synonymous	Exon 26 of 26	ENSP00000503830.2	Q9HCF6-3
	TRPM3	ENST00000377110.9	TSL:1	c.4689G>A	p.Ala1563Ala	synonymous	Exon 25 of 25	ENSP00000366314.4	Q9HCF6-2
	TRPM3	ENST00000377111.8	TSL:1	c.3955+734G>A		intron	N/A	ENSP00000366315.4	Q9HCF6-10

Frequencies

GnomAD3 genomes AF: 0.000480 AC: 73 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000235 AC: 59 AN: 251454 AF XY: 0.000206

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000112 AC: 164 AN: 1461850 Hom.: 0 Cov.: 82 AF XY: 0.000120 AC XY: 87 AN XY: 727216

African (AFR) AF: 0.00122 AC: 41 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000674 AC: 75 AN: 1111976

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.000417 AC XY: 31 AN XY: 74354

African (AFR) AF: 0.00125 AC: 52 AN: 41516

American (AMR) AF: 0.000655 AC: 10 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68010

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000186 Hom.: 0

Bravo AF: 0.000378

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.52
DANN	Benign	0.31
PhyloP100		-1.2
Mutation Taster		=98/2	polymorphism

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: rs138910787; hg19: chr9-73151304; COSMIC: COSV62591970;