9-93452218-G-T

Variant names:

• chr9-93452218-G-T
• rs1416988256
• NM_014612.5:c.303G>T

Variant summary

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

The NM_014612.5(FAM120A):​c.303G>T​(p.Glu101Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,272 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: 0.0000021 (0 hom.)
• Consequence: FAM120A NM_014612.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07

Genes affected

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]

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]

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=0.28842598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120A	NM_014612.5	c.303G>T	p.Glu101Asp	missense_variant	Exon 1 of 18	ENST00000277165.11	NP_055427.2
FAM120AOS	NM_198841.4	c.492C>A	p.Phe164Leu	missense_variant	Exon 1 of 3	ENST00000375412.11	NP_942138.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM120A	ENST00000277165.11	c.303G>T	p.Glu101Asp	missense_variant	Exon 1 of 18	1	NM_014612.5	ENSP00000277165.5
FAM120AOS	ENST00000375412.11	c.492C>A	p.Phe164Leu	missense_variant	Exon 1 of 3	1	NM_198841.4	ENSP00000364561.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000125 AC: 3 AN: 240046 Hom.: 0 AF XY: 0.0000228 AC XY: 3 AN XY: 131596

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000168

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459272 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 725902

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.492C>A (p.F164L) alteration is located in exon 1 (coding exon 1) of the FAM120AOS gene. This alteration results from a C to A substitution at nucleotide position 492, causing the phenylalanine (F) at amino acid position 164 to be replaced by a leucine (L). 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	Benign	0.33
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.79	T
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.093
Sift	Benign	0.38	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.34	B;D
Vest4		0.23
MutPred		0.39		Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);
MVP		0.26
MPC		0.96
ClinPred		0.97	D
GERP RS		3.8
Varity_R		0.38
gMVP		0.81

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: rs1416988256; hg19: chr9-96214500;