9-83534695-T-C

Position:

• chr9-83534695-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+3390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,072 control chromosomes in the GnomAD database, including 13,873 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 0.42 (13873 hom., cov: 32)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.147+3390A>G		intron_variant		ENST00000304195.8	NP_777598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD3	ENST00000304195.8	c.147+3390A>G		intron_variant		1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000376438.5	c.147+3390A>G		intron_variant		2		ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63328 AN: 151954 Hom.: 13857 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.417 AC: 63369 AN: 152072 Hom.: 13873 Cov.: 32 AF XY: 0.419 AC XY: 31110 AN XY: 74336

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.388

Alfa AF: 0.446 Hom.: 14542

Bravo AF: 0.406

Asia WGS AF: 0.424 AC: 1476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.50

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: rs7849075; hg19: chr9-86149610;