rs757124319

Variant names:

• chr6-75312759-G-A
• rs757124319
• NM_015687.5:c.3073C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-75312759-G-A
• chr6-75312759-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015687.5(FILIP1):​c.3073C>T​(p.Pro1025Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,614,086 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (1 hom.)
• Consequence: FILIP1 NM_015687.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• Publications: 0 publications found

Genes affected

FILIP1 (HGNC:21015): (filamin A interacting protein 1) This gene encodes a filamin A binding protein. The encoded protein promotes the degradation of filamin A and may regulate cortical neuron migration and dendritic spine morphology. Mice lacking a functional copy of this gene exhibit reduced dendritic spine length and altered excitatory signaling. [provided by RefSeq, Oct 2016]

TMEM30A-DT (HGNC:48985): (TMEM30A divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.104004115).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015687.5. 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
	FILIP1	NM_015687.5	MANE Select	c.3073C>T	p.Pro1025Ser	missense	Exon 5 of 6	NP_056502.1	Q7Z7B0-1
	FILIP1	NM_001289987.3		c.3082C>T	p.Pro1028Ser	missense	Exon 6 of 7	NP_001276916.1
	FILIP1	NM_001300866.3		c.3073C>T	p.Pro1025Ser	missense	Exon 5 of 7	NP_001287795.1	Q7Z7B0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FILIP1	ENST00000237172.12	TSL:1 MANE Select	c.3073C>T	p.Pro1025Ser	missense	Exon 5 of 6	ENSP00000237172.7	Q7Z7B0-1
	FILIP1	ENST00000393004.6	TSL:1	c.3073C>T	p.Pro1025Ser	missense	Exon 5 of 7	ENSP00000376728.1	Q7Z7B0-2
	FILIP1	ENST00000370020.1	TSL:1	c.2776C>T	p.Pro926Ser	missense	Exon 3 of 4	ENSP00000359037.1	A0A075B6G6

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251334 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461894 Hom.: 1 Cov.: 35 AF XY: 0.0000275 AC XY: 20 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152192 Hom.: 1 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

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	0.076
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.024
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	M
PhyloP100		4.6
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.061
Sift	Benign	0.092	T
Sift4G	Benign	0.093	T
Polyphen		0.18	B
Vest4		0.10
MutPred		0.24		Gain of phosphorylation at P1025 (P = 0.0321)
MVP		0.58
MPC		0.22
ClinPred		0.29	T
GERP RS		5.2
Varity_R		0.096
gMVP		0.44
Mutation Taster		=71/29	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: rs757124319; hg19: chr6-76022475; COSMIC: COSV105101925;