Variant 22-45328061-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017911.4(FAM118A):c.520A>G(p.Lys174Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM118A
NM_017911.4 missense, splice_region

Scores

Splicing: ADA: 0.06511

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.53

Variant links:

Genes affected

FAM118A (HGNC:1313): (family with sequence similarity 118 member A) Enables identical protein binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM118A links:

FAM118A (HGNC:):

FAM118A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM118A	NM_017911.4 linkuse as main transcript	c.520A>G	p.Lys174Glu	missense_variant, splice_region_variant	4/9	ENST00000441876.7	NP_060381.2	Q9NWS6-1A0A024R4V3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM118A	ENST00000441876.7 linkuse as main transcript	c.520A>G	p.Lys174Glu	missense_variant, splice_region_variant	4/9	1	NM_017911.4	ENSP00000395892.2	Q9NWS6-1
FAM118A	ENST00000216214.7 linkuse as main transcript	c.520A>G	p.Lys174Glu	missense_variant, splice_region_variant	5/10	2		ENSP00000216214.3	Q9NWS6-1
FAM118A	ENST00000405673.5 linkuse as main transcript	c.520A>G	p.Lys174Glu	missense_variant, splice_region_variant	4/5	5		ENSP00000385231.1	B0QY29
FAM118A	ENST00000477714.1 linkuse as main transcript	n.576A>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

656990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

347168

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.520A>G (p.K174E) alteration is located in exon 5 (coding exon 3) of the FAM118A gene. This alteration results from a A to G substitution at nucleotide position 520, causing the lysine (K) at amino acid position 174 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.086

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;T;.

Eigen

Benign

0.015

Eigen_PC

Benign

0.095

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.46

T;T;D

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

N;N;D

REVEL

Benign

0.19

Sift

Benign

0.16

T;T;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.49

P;P;.

Vest4

0.71

MutPred

0.47

Loss of MoRF binding (P = 0.0079);Loss of MoRF binding (P = 0.0079);Loss of MoRF binding (P = 0.0079);

MVP

0.27

MPC

0.35

ClinPred

0.79

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.20

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.065

dbscSNV1_RF

Benign

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over