9-83290751-A-G

Variant names:

• chr9-83290751-A-G
• rs942283
• NM_174938.6:c.1071-24T>C

Variant summary

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

The ENST00000376434.5(FRMD3):​c.489-24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,582,842 control chromosomes in the GnomAD database, including 304,829 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 0.55 (24391 hom., cov: 32)
  • Exomes 𝑓: 0.62 (280438 hom.)
• Consequence: FRMD3 ENST00000376434.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

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 (SAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.1071-24T>C		intron_variant	Intron 12 of 13	ENST00000304195.8	NP_777598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD3	ENST00000304195.8	c.1071-24T>C		intron_variant	Intron 12 of 13	1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000621208.4	c.939-24T>C		intron_variant	Intron 12 of 13	1		ENSP00000484839.1
FRMD3	ENST00000376434.5	c.489-24T>C		intron_variant	Intron 7 of 9	1		ENSP00000365617.1
FRMD3	ENST00000376438.5	c.1071-24T>C		intron_variant	Intron 12 of 14	2		ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83269 AN: 151888 Hom.: 24374 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.582

GnomAD2 exomes AF: 0.639 AC: 145485 AN: 227692 AF XY: 0.649

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.665

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.702

Gnomad FIN exome AF: 0.698

Gnomad NFE exome AF: 0.624

Gnomad OTH exome AF: 0.631

GnomAD4 exome AF: 0.622 AC: 890292 AN: 1430836 Hom.: 280438 Cov.: 36 AF XY: 0.628 AC XY: 444594 AN XY: 708368

African (AFR) AF: 0.317 AC: 10295 AN: 32426

American (AMR) AF: 0.652 AC: 27054 AN: 41476

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 13418 AN: 23962

East Asian (EAS) AF: 0.702 AC: 27609 AN: 39320

South Asian (SAS) AF: 0.787 AC: 64088 AN: 81472

European-Finnish (FIN) AF: 0.692 AC: 36202 AN: 52316

Middle Eastern (MID) AF: 0.665 AC: 3696 AN: 5560

European-Non Finnish (NFE) AF: 0.614 AC: 672003 AN: 1095336

Other (OTH) AF: 0.609 AC: 35927 AN: 58968

GnomAD4 genome AF: 0.548 AC: 83306 AN: 152006 Hom.: 24391 Cov.: 32 AF XY: 0.555 AC XY: 41231 AN XY: 74300

African (AFR) AF: 0.333 AC: 13790 AN: 41468

American (AMR) AF: 0.580 AC: 8873 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1954 AN: 3468

East Asian (EAS) AF: 0.689 AC: 3552 AN: 5154

South Asian (SAS) AF: 0.781 AC: 3761 AN: 4814

European-Finnish (FIN) AF: 0.689 AC: 7268 AN: 10542

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 42007 AN: 67952

Other (OTH) AF: 0.586 AC: 1239 AN: 2114

Alfa AF: 0.570 Hom.: 6430

Bravo AF: 0.528

Asia WGS AF: 0.754 AC: 2618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.79
DANN	Benign	0.29
PhyloP100		-0.34
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

Publications

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Other links and lift over

dbSNP: rs942283; hg19: chr9-85905666; COSMIC: COSV58455006;