9-83299328-A-T

Variant names:

• chr9-83299328-A-T
• rs1359168
• NM_174938.6:c.927-142T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174938.6(FRMD3):​c.927-142T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 431,132 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	NM_174938.6	MANE Select	c.927-142T>A		intron	N/A	NP_777598.3
	FRMD3	NM_001244959.2		c.927-142T>A		intron	N/A	NP_001231888.1	A2A2Y4-2
	FRMD3	NM_001244960.2		c.795-142T>A		intron	N/A	NP_001231889.1	A2A2Y4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD3	ENST00000304195.8	TSL:1 MANE Select	c.927-142T>A		intron	N/A	ENSP00000303508.3	A2A2Y4-1
	FRMD3	ENST00000621208.4	TSL:1	c.795-142T>A		intron	N/A	ENSP00000484839.1	A2A2Y4-5
	FRMD3	ENST00000376434.5	TSL:1	c.345-142T>A		intron	N/A	ENSP00000365617.1	A2A2Y4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000232 AC: 1 AN: 431132 Hom.: 0 AF XY: 0.00000441 AC XY: 1 AN XY: 226616

African (AFR) AF: 0.00 AC: 0 AN: 11050

American (AMR) AF: 0.00 AC: 0 AN: 12532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13412

East Asian (EAS) AF: 0.00 AC: 0 AN: 28712

South Asian (SAS) AF: 0.0000262 AC: 1 AN: 38210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 261168

Other (OTH) AF: 0.00 AC: 0 AN: 24950

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.40
PhyloP100		-0.64

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: rs1359168; hg19: chr9-85914243;