chr6-75312516-C-T

Variant names:

• chr6-75312516-C-T
• rs374887916
• NM_015687.5:c.3316G>A

Variant summary

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

The NM_015687.5(FILIP1):​c.3316G>A​(p.Gly1106Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,880 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: FILIP1 NM_015687.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

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

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=0.2710566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FILIP1	NM_015687.5	c.3316G>A	p.Gly1106Ser	missense_variant	Exon 5 of 6	ENST00000237172.12	NP_056502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FILIP1	ENST00000237172.12	c.3316G>A	p.Gly1106Ser	missense_variant	Exon 5 of 6	1	NM_015687.5	ENSP00000237172.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251476 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135914

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461880 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.6	D;N;D
REVEL	Benign	0.19
Sift	Benign	0.043	D;D;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.90	P;P;.
Vest4		0.26
MutPred		0.068		Gain of glycosylation at G1106 (P = 0.0269);Gain of glycosylation at G1106 (P = 0.0269);.;
MVP		0.71
MPC		0.40
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.25
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs374887916; hg19: chr6-76022232;