9-83532035-T-C

Variant names:

• chr9-83532035-T-C
• rs4877788
• NM_174938.6:c.147+6050A>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+6050A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,036 control chromosomes in the GnomAD database, including 29,993 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 0.62 (29993 hom., cov: 32)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174938.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	NM_174938.6	MANE Select	c.147+6050A>G		intron	N/A	NP_777598.3
	FRMD3	NM_001244959.2		c.147+6050A>G		intron	N/A	NP_001231888.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.147+6050A>G		intron	N/A	ENSP00000303508.3
	FRMD3	ENST00000376438.5	TSL:2	c.147+6050A>G		intron	N/A	ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94887 AN: 151918 Hom.: 29968 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.625 AC: 94947 AN: 152036 Hom.: 29993 Cov.: 32 AF XY: 0.621 AC XY: 46154 AN XY: 74310

African (AFR) AF: 0.667 AC: 27659 AN: 41476

American (AMR) AF: 0.603 AC: 9212 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2365 AN: 3472

East Asian (EAS) AF: 0.336 AC: 1736 AN: 5172

South Asian (SAS) AF: 0.523 AC: 2521 AN: 4824

European-Finnish (FIN) AF: 0.635 AC: 6694 AN: 10548

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42740 AN: 67948

Other (OTH) AF: 0.653 AC: 1374 AN: 2104

Alfa AF: 0.623 Hom.: 12730

Bravo AF: 0.626

Asia WGS AF: 0.484 AC: 1688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		-0.055
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: rs4877788; hg19: chr9-86146950; COSMIC: COSV58458474;