12-8221980-A-T

Variant names:

• chr12-8221980-A-T
• NM_018088.3:c.1237T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018088.3(FAM90A1):​c.1237T>A​(p.Ser413Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FAM90A1 NM_018088.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.199

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06674242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM90A1	NM_018088.3	c.1237T>A	p.Ser413Thr	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.1237T>A	p.Ser413Thr	missense_variant	Exon 7 of 7	1	NM_018088.3	ENSP00000445418.1
FAM90A1	ENST00000307435.10	c.1237T>A	p.Ser413Thr	missense_variant	Exon 6 of 6	2		ENSP00000307798.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1237T>A (p.S413T) alteration is located in exon 7 (coding exon 4) of the FAM90A1 gene. This alteration results from a T to A substitution at nucleotide position 1237, causing the serine (S) at amino acid position 413 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.6
DANN	Benign	0.81
DEOGEN2	Benign	0.0021	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.34	.;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.16	N;N
REVEL	Benign	0.033
Sift	Benign	0.49	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.45	B;B
Vest4		0.12
MutPred		0.34		Gain of glycosylation at S413 (P = 0.0182);Gain of glycosylation at S413 (P = 0.0182);
MVP		0.15
MPC		0.36
ClinPred		0.14	T
GERP RS		-0.84
Varity_R		0.13
gMVP		0.025

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: chr12-8374576;