9-37692736-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014907.3(FRMPD1):​c.95C>T​(p.Ser32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000807 in 1,610,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: FRMPD1 NM_014907.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.017974347).

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.95C>T	p.Ser32Leu	missense	Exon 2 of 16	NP_055722.2	Q5SYB0-1
	FRMPD1	NM_001371223.1		c.95C>T	p.Ser32Leu	missense	Exon 2 of 16	NP_001358152.1	Q5SYB0-1
	FRMPD1	NM_001371224.1		c.95C>T	p.Ser32Leu	missense	Exon 3 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.95C>T	p.Ser32Leu	missense	Exon 2 of 16	ENSP00000366995.3	Q5SYB0-1
	FRMPD1	ENST00000539465.5	TSL:1	c.95C>T	p.Ser32Leu	missense	Exon 2 of 16	ENSP00000444411.1	Q5SYB0-1
	ENSG00000255872	ENST00000540557.1	TSL:5	n.*1135+406G>A		intron	N/A	ENSP00000457548.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000160 AC: 40 AN: 250418 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00319

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000747 AC: 109 AN: 1458238 Hom.: 0 Cov.: 29 AF XY: 0.0000675 AC XY: 49 AN XY: 725736

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00287 AC: 75 AN: 26122

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1108720

Other (OTH) AF: 0.000149 AC: 9 AN: 60274

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000111 Hom.: 0

Bravo AF: 0.000117

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.00

EpiControl AF: 0.000119

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	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0036	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.11	T
Polyphen		0.82	P
Vest4		0.37
MVP		0.44
MPC		0.16
ClinPred		0.13	T
GERP RS		5.5
Varity_R		0.20
gMVP		0.44
Mutation Taster		=88/12	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

dbSNP: rs3747540; hg19: chr9-37692733; COSMIC: COSV63383141;