rs3860941

Variant names:

• chr9-83493750-G-A
• rs3860941
• NM_174938.6:c.147+44335C>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+44335C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,034 control chromosomes in the GnomAD database, including 18,625 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 0.49 (18625 hom., cov: 32)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.147+44335C>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+44335C>T		intron_variant	Intron 1 of 13	1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000376438.5	c.147+44335C>T		intron_variant	Intron 1 of 14	2		ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74273 AN: 151916 Hom.: 18616 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.0867

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.489 AC: 74316 AN: 152034 Hom.: 18625 Cov.: 32 AF XY: 0.485 AC XY: 36041 AN XY: 74326

African (AFR) AF: 0.492 AC: 20399 AN: 41468

American (AMR) AF: 0.512 AC: 7814 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1956 AN: 3468

East Asian (EAS) AF: 0.0865 AC: 447 AN: 5166

South Asian (SAS) AF: 0.413 AC: 1992 AN: 4822

European-Finnish (FIN) AF: 0.474 AC: 5008 AN: 10568

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35092 AN: 67958

Other (OTH) AF: 0.519 AC: 1096 AN: 2112

Alfa AF: 0.504 Hom.: 83587

Bravo AF: 0.493

Asia WGS AF: 0.337 AC: 1179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.57
PhyloP100		-2.0
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: rs3860941; hg19: chr9-86108665;