9-83292601-A-G

Variant names:

• chr9-83292601-A-G
• rs10867977
• NM_174938.6:c.1071-1874T>C

Variant summary

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

The NM_174938.6(FRMD3):​c.1071-1874T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,164 control chromosomes in the GnomAD database, including 24,684 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 (24684 hom., cov: 33)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.1071-1874T>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.1071-1874T>C		intron_variant	Intron 12 of 13	1	NM_174938.6	ENSP00000303508.3
FRMD3	ENST00000621208.4	c.939-1874T>C		intron_variant	Intron 12 of 13	1		ENSP00000484839.1
FRMD3	ENST00000376434.5	c.489-1874T>C		intron_variant	Intron 7 of 9	1		ENSP00000365617.1
FRMD3	ENST00000376438.5	c.1071-1874T>C		intron_variant	Intron 12 of 14	2		ENSP00000365621.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83970 AN: 152046 Hom.: 24667 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.552 AC: 84008 AN: 152164 Hom.: 24684 Cov.: 33 AF XY: 0.557 AC XY: 41473 AN XY: 74398

African (AFR) AF: 0.337 AC: 13987 AN: 41498

American (AMR) AF: 0.591 AC: 9035 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3701 AN: 5176

South Asian (SAS) AF: 0.728 AC: 3507 AN: 4818

European-Finnish (FIN) AF: 0.681 AC: 7221 AN: 10598

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42503 AN: 67990

Other (OTH) AF: 0.585 AC: 1233 AN: 2108

Alfa AF: 0.596 Hom.: 10215

Bravo AF: 0.535

Asia WGS AF: 0.736 AC: 2554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.61
PhyloP100		-0.68
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: rs10867977; hg19: chr9-85907516;