NM_174938.6:c.147+66113A>G

Variant names:

• chr9-83471972-T-C
• rs17086298
• NM_174938.6:c.147+66113A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.147+66113A>G		intron_variant	Intron 1 of 13	ENST00000304195.8	NP_777598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD3	ENST00000304195.8	c.147+66113A>G		intron_variant	Intron 1 of 13	1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000376438.5	c.147+66113A>G		intron_variant	Intron 1 of 14	2		ENSP00000365621.1

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

African (AFR) AF: 0.0140 AC: 581 AN: 41570

American (AMR) AF: 0.0458 AC: 701 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3472

East Asian (EAS) AF: 0.152 AC: 788 AN: 5168

South Asian (SAS) AF: 0.115 AC: 557 AN: 4830

European-Finnish (FIN) AF: 0.145 AC: 1533 AN: 10598

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0631 AC: 4292 AN: 68016

Other (OTH) AF: 0.0493 AC: 104 AN: 2108

Alfa AF: 0.0591 Hom.: 505

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
PhyloP100		0.0070
Mutation Taster		=100/0	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: rs17086298; hg19: chr9-86086887;