rs10868008

chr9-83436354-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174938.6(FRMD3):c.148-46646T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 152,184 control chromosomes in the GnomAD database, including 612 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 0.084 (612 hom., cov: 31)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD3	NM_174938.6	c.148-46646T>G		intron_variant		ENST00000304195.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD3	ENST00000304195.8	c.148-46646T>G		intron_variant		1	NM_174938.6	P1
FRMD3	ENST00000621208.4	c.15+31264T>G		intron_variant		1
FRMD3	ENST00000376438.5	c.148-46646T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0840 AC: 12767 AN: 152066 Hom.: 615 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0621

Gnomad ASJ AF: 0.0707

Gnomad EAS AF: 0.0941

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0759

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

GnomAD4 genome AF: 0.0839 AC: 12766 AN: 152184 Hom.: 612 Cov.: 31 AF XY: 0.0857 AC XY: 6373 AN XY: 74388

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.0707

Gnomad4 EAS AF: 0.0941

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0589

Gnomad4 NFE AF: 0.0687

Gnomad4 OTH AF: 0.0751

Alfa AF: 0.0789 Hom.: 280

Bravo AF: 0.0816

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.7
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs10868008; hg19: chr9-86051269;