9-83280504-A-G

Variant names:

• chr9-83280504-A-G
• rs10867970
• NM_174938.6:c.1195+10099T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174938.6(FRMD3):​c.1195+10099T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,292 control chromosomes in the GnomAD database, including 609 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 0.056 (609 hom., cov: 32)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 0 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]

LOC124902190 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.1195+10099T>C		intron	N/A	NP_777598.3
	FRMD3	NM_001244959.2		c.1195+10099T>C		intron	N/A	NP_001231888.1
	FRMD3	NM_001244960.2		c.1063+10099T>C		intron	N/A	NP_001231889.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.1195+10099T>C		intron	N/A	ENSP00000303508.3
	FRMD3	ENST00000621208.4	TSL:1	c.1063+10099T>C		intron	N/A	ENSP00000484839.1
	FRMD3	ENST00000376434.5	TSL:1	c.613+10099T>C		intron	N/A	ENSP00000365617.1

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8450 AN: 152174 Hom.: 607 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00980

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0555 AC: 8458 AN: 152292 Hom.: 609 Cov.: 32 AF XY: 0.0549 AC XY: 4092 AN XY: 74478

African (AFR) AF: 0.171 AC: 7096 AN: 41524

American (AMR) AF: 0.0220 AC: 337 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5180

South Asian (SAS) AF: 0.0292 AC: 141 AN: 4828

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00977 AC: 665 AN: 68036

Other (OTH) AF: 0.0364 AC: 77 AN: 2116

Alfa AF: 0.0241 Hom.: 626

Bravo AF: 0.0622

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		0.031
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: rs10867970; hg19: chr9-85895419;