22-45328055-A-G

Position:

• chr22-45328055-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017911.4(FAM118A):​c.514A>G​(p.Lys172Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM118A NM_017911.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10018623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM118A	NM_017911.4	c.514A>G	p.Lys172Glu	missense_variant	4/9	ENST00000441876.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM118A	ENST00000441876.7	c.514A>G	p.Lys172Glu	missense_variant	4/9	1	NM_017911.4	P1
FAM118A	ENST00000216214.7	c.514A>G	p.Lys172Glu	missense_variant	5/10	2		P1
FAM118A	ENST00000405673.5	c.514A>G	p.Lys172Glu	missense_variant	4/5	5
FAM118A	ENST00000477714.1	n.570A>G		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1010682 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 515624

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.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 22, 2023

The c.514A>G (p.K172E) 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 514, causing the lysine (K) at amino acid position 172 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	0.39
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0070	T;T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.050	N;N;N
REVEL	Benign	0.092
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.20	B;B;.
Vest4		0.14
MutPred		0.34		Loss of MoRF binding (P = 0.0169);Loss of MoRF binding (P = 0.0169);Loss of MoRF binding (P = 0.0169);
MVP		0.12
MPC		0.33
ClinPred		0.80	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.16
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-45723936;