15-43874320-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_032892.5(FRMD5):c.1278T>C(p.Pro426=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,614,184 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (79 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (88 hom.)
• Consequence: FRMD5 NM_032892.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.12

Genes affected

FRMD5 (HGNC:28214): (FERM domain containing 5) Enables integrin binding activity and protein kinase binding activity. Involved in negative regulation of cell motility; positive regulation of cell adhesion; and regulation of cell migration. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 15-43874320-A-G is Benign according to our data. Variant chr15-43874320-A-G is described in ClinVar as [Benign]. Clinvar id is 714651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMD5	NM_032892.5	c.1278T>C	p.Pro426=	synonymous_variant	14/14	ENST00000417257.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMD5	ENST00000417257.6	c.1278T>C	p.Pro426=	synonymous_variant	14/14	1	NM_032892.5	P1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2758 AN: 152194 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00462 AC: 1159 AN: 250944 Hom.: 37 AF XY: 0.00349 AC XY: 473 AN XY: 135658

Gnomad AFR exome AF: 0.0646

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00181 AC: 2640 AN: 1461872 Hom.: 88 Cov.: 32 AF XY: 0.00156 AC XY: 1132 AN XY: 727242

Gnomad4 AFR exome AF: 0.0651

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000270

Gnomad4 OTH exome AF: 0.00455

GnomAD4 genome AF: 0.0182 AC: 2776 AN: 152312 Hom.: 79 Cov.: 32 AF XY: 0.0174 AC XY: 1298 AN XY: 74490

Gnomad4 AFR AF: 0.0634

Gnomad4 AMR AF: 0.00699

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00751 Hom.: 16

Bravo AF: 0.0202

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.51
Dann	Benign	0.71

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: rs61735012; hg19: chr15-44166518;