rs17086298

chr9-83471972-T-C

Variant summary

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

The NM_174938.6(FRMD3):c.147+66113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 152,262 control chromosomes in the GnomAD database, including 428 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 0.059 (428 hom., cov: 33)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

Genes affected

FRMD3 (HGNC:24125): (FERM domain containing 3) The protein encoded by this gene is a single pass membrane protein primarily found in ovaries. A similar protein in erythrocytes helps determine the shape of red blood cells, but the function of the encoded protein has not been determined. There is some evidence that this is a tumor suppressor gene, and there is also evidence linking defects in this gene to susceptibility to diabetic nephropathy in type 1 diabetes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD3	NM_174938.6	c.147+66113A>G		intron_variant		ENST00000304195.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD3	ENST00000304195.8	c.147+66113A>G		intron_variant		1	NM_174938.6	P1
FRMD3	ENST00000376438.5	c.147+66113A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9017 AN: 152144 Hom.: 430 Cov.: 33

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0494

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

GnomAD4 genome AF: 0.0592 AC: 9014 AN: 152262 Hom.: 428 Cov.: 33 AF XY: 0.0644 AC XY: 4795 AN XY: 74444

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0458

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0631

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0620 Hom.: 431

Bravo AF: 0.0484

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.9
Dann	Benign	0.78

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: rs17086298; hg19: chr9-86086887;