9-37692724-C-G

Variant names:

• chr9-37692724-C-G
• rs896563867
• NM_014907.3:c.83C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014907.3(FRMPD1):​c.83C>G​(p.Ser28Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FRMPD1 NM_014907.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3796643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD1	NM_014907.3	c.83C>G	p.Ser28Cys	missense_variant	Exon 2 of 16	ENST00000377765.8	NP_055722.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD1	ENST00000377765.8	c.83C>G	p.Ser28Cys	missense_variant	Exon 2 of 16	1	NM_014907.3	ENSP00000366995.3
FRMPD1	ENST00000539465.5	c.83C>G	p.Ser28Cys	missense_variant	Exon 2 of 16	1		ENSP00000444411.1
ENSG00000255872	ENST00000540557.1	n.*1135+418G>C		intron_variant	Intron 11 of 11	5		ENSP00000457548.1
FRMPD1	ENST00000359927.3	c.83C>G	p.Ser28Cys	missense_variant	Exon 2 of 3	3		ENSP00000439868.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.83C>G (p.S28C) alteration is located in exon 2 (coding exon 1) of the FRMPD1 gene. This alteration results from a C to G substitution at nucleotide position 83, causing the serine (S) at amino acid position 28 to be replaced by a cysteine (C). 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	Benign	0.33
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	.;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.0	N;N;D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.56
MutPred		0.35		Loss of phosphorylation at S28 (P = 0.0037);Loss of phosphorylation at S28 (P = 0.0037);Loss of phosphorylation at S28 (P = 0.0037);
MVP		0.81
MPC		0.61
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.44
gMVP		0.50

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: rs896563867; hg19: chr9-37692721;