rs3860922

Variant names:

• chr9-83433968-G-T
• rs3860922
• NM_174938.6:c.148-44260C>A

Variant summary

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

The NM_174938.6(FRMD3):​c.148-44260C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 152,228 control chromosomes in the GnomAD database, including 411 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 0.068 (411 hom., cov: 32)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 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.148-44260C>A		intron	N/A	NP_777598.3
	FRMD3	NM_001244959.2		c.148-44260C>A		intron	N/A	NP_001231888.1
	FRMD3	NM_001244960.2		c.15+33650C>A		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.148-44260C>A		intron	N/A	ENSP00000303508.3
	FRMD3	ENST00000621208.4	TSL:1	c.15+33650C>A		intron	N/A	ENSP00000484839.1
	FRMD3	ENST00000376438.5	TSL:2	c.148-44260C>A		intron	N/A	ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10294 AN: 152110 Hom.: 412 Cov.: 32

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0718

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

GnomAD4 genome AF: 0.0677 AC: 10311 AN: 152228 Hom.: 411 Cov.: 32 AF XY: 0.0709 AC XY: 5276 AN XY: 74416

African (AFR) AF: 0.0291 AC: 1208 AN: 41560

American (AMR) AF: 0.0478 AC: 731 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.160 AC: 824 AN: 5166

South Asian (SAS) AF: 0.0922 AC: 444 AN: 4818

European-Finnish (FIN) AF: 0.128 AC: 1351 AN: 10580

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0780 AC: 5307 AN: 68018

Other (OTH) AF: 0.0720 AC: 152 AN: 2112

Alfa AF: 0.0738 Hom.: 1249

Bravo AF: 0.0588

Asia WGS AF: 0.103 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.68
PhyloP100		-2.6
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: rs3860922; hg19: chr9-86048883;