9-83495365-G-A

Variant names:

• chr9-83495365-G-A
• rs4097644
• NM_174938.6:c.147+42720C>T

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+42720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,982 control chromosomes in the GnomAD database, including 19,436 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 0.50 (19436 hom., cov: 32)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.147+42720C>T		intron_variant	Intron 1 of 13	ENST00000304195.8	NP_777598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMD3	ENST00000304195.8	c.147+42720C>T		intron_variant	Intron 1 of 13	1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000376438.5	c.147+42720C>T		intron_variant	Intron 1 of 14	2		ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75772 AN: 151864 Hom.: 19424 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.0859

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.499 AC: 75822 AN: 151982 Hom.: 19436 Cov.: 32 AF XY: 0.494 AC XY: 36715 AN XY: 74264

African (AFR) AF: 0.525 AC: 21748 AN: 41440

American (AMR) AF: 0.515 AC: 7869 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1958 AN: 3464

East Asian (EAS) AF: 0.0857 AC: 444 AN: 5180

South Asian (SAS) AF: 0.413 AC: 1989 AN: 4814

European-Finnish (FIN) AF: 0.476 AC: 5017 AN: 10540

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35180 AN: 67962

Other (OTH) AF: 0.523 AC: 1104 AN: 2110

Alfa AF: 0.509 Hom.: 11135

Bravo AF: 0.504

Asia WGS AF: 0.331 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4097644; hg19: chr9-86110280;