12-8222093-G-A

Variant names:

• chr12-8222093-G-A
• NM_018088.3:c.1124C>T

Variant summary

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

The NM_018088.3(FAM90A1):​c.1124C>T​(p.Ala375Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM90A1 NM_018088.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

Genes affected

FAM90A1 (HGNC:25526): (family with sequence similarity 90 member A1) FAM90A1 belongs to subfamily I of the primate-specific FAM90A gene family, which originated from multiple duplications and rearrangements (Bosch et al., 2007 [PubMed 17684299]).[supplied by OMIM, Oct 2009]

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=0.19469178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM90A1	NM_018088.3	c.1124C>T	p.Ala375Val	missense_variant	Exon 7 of 7	ENST00000538603.6	NP_060558.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM90A1	ENST00000538603.6	c.1124C>T	p.Ala375Val	missense_variant	Exon 7 of 7	1	NM_018088.3	ENSP00000445418.1
FAM90A1	ENST00000307435.10	c.1124C>T	p.Ala375Val	missense_variant	Exon 6 of 6	2		ENSP00000307798.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457754 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725286

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1124C>T (p.A375V) alteration is located in exon 7 (coding exon 4) of the FAM90A1 gene. This alteration results from a C to T substitution at nucleotide position 1124, causing the alanine (A) at amino acid position 375 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0063	T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.065
Sift	Benign	0.082	T;T
Sift4G	Benign	0.12	T;T
Polyphen		1.0	D;D
Vest4		0.24
MutPred		0.18		Loss of glycosylation at S379 (P = 0.1003);Loss of glycosylation at S379 (P = 0.1003);
MVP		0.37
MPC		0.68
ClinPred		0.69	D
GERP RS		-0.72
Varity_R		0.050
gMVP		0.049

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr12-8374689;