9-37719089-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD1	NM_014907.3	c.429C>A	p.Phe143Leu	missense_variant	Exon 6 of 16	ENST00000377765.8	NP_055722.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD1	ENST00000377765.8	c.429C>A	p.Phe143Leu	missense_variant	Exon 6 of 16	1	NM_014907.3	ENSP00000366995.3
FRMPD1	ENST00000539465.5	c.429C>A	p.Phe143Leu	missense_variant	Exon 6 of 16	1		ENSP00000444411.1
ENSG00000255872	ENST00000540557.1	n.*1011+8839G>T		intron_variant	Intron 10 of 11	5		ENSP00000457548.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.429C>A (p.F143L) alteration is located in exon 6 (coding exon 5) of the FRMPD1 gene. This alteration results from a C to A substitution at nucleotide position 429, causing the phenylalanine (F) at amino acid position 143 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Benign	0.23
Sift	Benign	0.059	T;T
Sift4G	Uncertain	0.030	D;D
Polyphen		0.99	D;D
Vest4		0.67
MutPred		0.34		Gain of ubiquitination at K140 (P = 0.0817);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-37719086;