9-109166961-C-T

Variant names:

• chr9-109166961-C-T
• rs772506414
• NM_014334.4:c.178G>A

Variant summary

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

The NM_014334.4(FRRS1L):​c.178G>A​(p.Asp60Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRRS1L NM_014334.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39

Genes affected

FRRS1L (HGNC:1362): (ferric chelate reductase 1 like) This gene encodes a component of the outer-core of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor protein in the brain. The encoded protein is thought to interact with inner-core components of the receptor, and play a role in the modulation of glutamate signaling. Mutations in this gene are associated with early infantile epileptic encephalopathy 37. [provided by RefSeq, Jul 2016]

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=0.32346565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRRS1L	NM_014334.4	c.178G>A	p.Asp60Asn	missense_variant	Exon 1 of 5	ENST00000561981.5	NP_055149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRRS1L	ENST00000561981.5	c.178G>A	p.Asp60Asn	missense_variant	Exon 1 of 5	1	NM_014334.4	ENSP00000477141.2
FRRS1L	ENST00000644747.1	n.43G>A		non_coding_transcript_exon_variant	Exon 1 of 4			ENSP00000493964.1
FRRS1L	ENST00000642299.1	n.-30G>A		upstream_gene_variant				ENSP00000495137.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1194926 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 581432

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.066
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.62	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.97	D
Sift4G	Benign	0.091	T
Polyphen		1.0	D
Vest4		0.23
MutPred		0.41		Loss of disorder (P = 0.107);
MVP		0.61
MPC		0.081
ClinPred		0.66	D
GERP RS		2.6
Varity_R		0.11
gMVP		0.19

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: rs772506414; hg19: chr9-111929241;