15-43874320-A-G

Variant names:

• chr15-43874320-A-G
• rs61735012
• NM_032892.5:c.1278T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032892.5(FRMD5):​c.1278T>C​(p.Pro426Pro) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.12
• Publications: 3 publications found

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]

FRMD5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with eye movement abnormalities and ataxia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 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 VariationId is 714651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032892.5. 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
	FRMD5	NM_032892.5	MANE Select	c.1278T>C	p.Pro426Pro	synonymous	Exon 14 of 14	NP_116281.2	Q7Z6J6-1
	FRMD5	NM_001411124.1		c.1278T>C	p.Pro426Pro	synonymous	Exon 14 of 15	NP_001398053.1	B5MC67
	FRMD5	NM_001322949.2		c.1278T>C	p.Pro426Pro	synonymous	Exon 14 of 16	NP_001309878.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD5	ENST00000417257.6	TSL:1 MANE Select	c.1278T>C	p.Pro426Pro	synonymous	Exon 14 of 14	ENSP00000403067.1	Q7Z6J6-1
	FRMD5	ENST00000421674.5	TSL:1	n.*1222T>C		non_coding_transcript_exon	Exon 15 of 15	ENSP00000401635.1	F8WEJ8
	FRMD5	ENST00000458630.5	TSL:1	n.*1225T>C		non_coding_transcript_exon	Exon 15 of 15	ENSP00000404496.1	H7C282

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

GnomAD2 exomes AF: 0.00462 AC: 1159 AN: 250944 AF XY: 0.00349

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 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

African (AFR) AF: 0.0651 AC: 2179 AN: 33478

American (AMR) AF: 0.00295 AC: 132 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1112008

Other (OTH) AF: 0.00455 AC: 275 AN: 60396

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

African (AFR) AF: 0.0634 AC: 2635 AN: 41558

American (AMR) AF: 0.00699 AC: 107 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68018

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.00751 Hom.: 18

Bravo AF: 0.0202

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.51
DANN	Benign	0.71
PhyloP100		-4.1
Mutation Taster		=98/2	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: rs61735012; hg19: chr15-44166518;