chr9-37719089-C-A

Variant names:

• chr9-37719089-C-A
• NM_014907.3:c.429C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014907.3(FRMPD1):​c.429C>A​(p.Phe143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FRMPD1 NM_014907.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.301
• Publications: 0 publications found

Genes affected

FRMPD1 (HGNC:29159): (FERM and PDZ domain containing 1) Involved in establishment of protein localization to membrane and regulation of G protein-coupled receptor signaling pathway. Located in plasma membrane. Part of protein-containing complex. Colocalizes with cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255872 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014907.3. 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
	FRMPD1	NM_014907.3	MANE Select	c.429C>A	p.Phe143Leu	missense	Exon 6 of 16	NP_055722.2	Q5SYB0-1
	FRMPD1	NM_001371223.1		c.429C>A	p.Phe143Leu	missense	Exon 6 of 16	NP_001358152.1	Q5SYB0-1
	FRMPD1	NM_001371224.1		c.429C>A	p.Phe143Leu	missense	Exon 7 of 17	NP_001358153.1	Q5SYB0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD1	ENST00000377765.8	TSL:1 MANE Select	c.429C>A	p.Phe143Leu	missense	Exon 6 of 16	ENSP00000366995.3	Q5SYB0-1
	FRMPD1	ENST00000539465.5	TSL:1	c.429C>A	p.Phe143Leu	missense	Exon 6 of 16	ENSP00000444411.1	Q5SYB0-1
	ENSG00000255872	ENST00000540557.1	TSL:5	n.*1011+8839G>T		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.30
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.23
Sift	Benign	0.059	T
Sift4G	Uncertain	0.030	D
Polyphen		0.99	D
Vest4		0.67
MutPred		0.34		Gain of ubiquitination at K140 (P = 0.0817)
MVP		0.57
MPC		0.67
ClinPred		0.98	D
GERP RS		2.8
Varity_R		0.56
gMVP		0.44
Mutation Taster		=72/28	polymorphism

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

hg19: chr9-37719086;