NM_198841.4:c.498C>G

Variant names:

• chr9-93452212-G-C
• rs1460804638
• NM_198841.4:c.498C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198841.4(FAM120AOS):​c.498C>G​(p.Ser166Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM120AOS NM_198841.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

Genes affected

FAM120AOS (HGNC:23389): (family with sequence similarity 120 member A opposite strand) Differences in the expression level of this gene are associated with the survival rate of those with glioma. [provided by RefSeq, May 2017]

FAM120A (HGNC:13247): (family with sequence similarity 120 member A) Enables RNA binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

FAM120A Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10821706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198841.4. 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
	FAM120AOS	NM_198841.4	MANE Select	c.498C>G	p.Ser166Arg	missense	Exon 1 of 3	NP_942138.2	Q5T036
	FAM120A	NM_014612.5	MANE Select	c.297G>C	p.Ala99Ala	synonymous	Exon 1 of 18	NP_055427.2
	FAM120A	NM_001439102.1		c.297G>C	p.Ala99Ala	synonymous	Exon 1 of 19	NP_001426031.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120AOS	ENST00000375412.11	TSL:1 MANE Select	c.498C>G	p.Ser166Arg	missense	Exon 1 of 3	ENSP00000364561.5	Q5T036
	FAM120A	ENST00000277165.11	TSL:1 MANE Select	c.297G>C	p.Ala99Ala	synonymous	Exon 1 of 18	ENSP00000277165.5	Q9NZB2-1
	FAM120A	ENST00000375389.7	TSL:1	c.297G>C	p.Ala99Ala	synonymous	Exon 1 of 9	ENSP00000364538.3	Q9NZB2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000417 AC: 1 AN: 239824 AF XY: 0.00

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: 0.00000939

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459250 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 725916

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111602

Other (OTH) AF: 0.00 AC: 0 AN: 60300

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	1.3	N
REVEL	Benign	0.052
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.24	T
Polyphen		0.098	B
Vest4		0.056
MutPred		0.21		Gain of MoRF binding (P = 0.005)
MVP		0.068
MPC		0.88
ClinPred		0.50	T
GERP RS		2.9
PromoterAI		0.061	Neutral
Varity_R		0.32
gMVP		0.053
Mutation Taster		=85/15	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: rs1460804638; hg19: chr9-96214494;