rs3747540

Variant names:

• chr9-37692736-C-G
• rs3747540
• NM_014907.3:c.95C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-37692736-C-G
• chr9-37692736-C-T

Variant summary

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

The NM_014907.3(FRMPD1):​c.95C>G​(p.Ser32Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S32L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FRMPD1 NM_014907.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36

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=0.3966162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD1	NM_014907.3	c.95C>G	p.Ser32Trp	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.95C>G	p.Ser32Trp	missense_variant	Exon 2 of 16	1	NM_014907.3	ENSP00000366995.3
FRMPD1	ENST00000539465.5	c.95C>G	p.Ser32Trp	missense_variant	Exon 2 of 16	1		ENSP00000444411.1
ENSG00000255872	ENST00000540557.1	n.*1135+406G>C		intron_variant	Intron 11 of 11	5		ENSP00000457548.1
FRMPD1	ENST00000359927.3	c.95C>G	p.Ser32Trp	missense_variant	Exon 2 of 3	3		ENSP00000439868.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458238 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725736

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	.;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.3	N;N;D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.58
MutPred		0.41		Loss of phosphorylation at S32 (P = 0.0055);Loss of phosphorylation at S32 (P = 0.0055);Loss of phosphorylation at S32 (P = 0.0055);
MVP		0.51
MPC		0.68
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.60

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: rs3747540; hg19: chr9-37692733;