1-231040123-C-T

Position:

• chr1-231040123-C-T

Variant summary

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

The NM_198552.3(FAM89A):​c.89G>A​(p.Ser30Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000403 in 1,240,878 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S30G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: FAM89A NM_198552.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

Genes affected

FAM89A (HGNC:25057): (family with sequence similarity 89 member A)

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=0.32016873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM89A	NM_198552.3	c.89G>A	p.Ser30Asn	missense_variant	1/2	ENST00000366654.5	NP_940954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM89A	ENST00000366654.5	c.89G>A	p.Ser30Asn	missense_variant	1/2	1	NM_198552.3	ENSP00000355614.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000234 AC: 2 AN: 85640 Hom.: 0 AF XY: 0.0000203 AC XY: 1 AN XY: 49344

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000581

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000403 AC: 5 AN: 1240878 Hom.: 0 Cov.: 31 AF XY: 0.00000164 AC XY: 1 AN XY: 610250

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: 0.00000500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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 17, 2023

The c.89G>A (p.S30N) alteration is located in exon 1 (coding exon 1) of the FAM89A gene. This alteration results from a G to A substitution at nucleotide position 89, causing the serine (S) at amino acid position 30 to be replaced by an asparagine (N). 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	Pathogenic	0.96
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.039	T
Eigen	Benign	0.063
Eigen_PC	Benign	-0.046
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Benign	0.030	D
Sift4G	Uncertain	0.018	D
Polyphen		0.94	P
Vest4		0.48
MutPred		0.21		Loss of glycosylation at S30 (P = 0.0077);
MVP		0.15
MPC		0.27
ClinPred		0.73	D
GERP RS		2.0
Varity_R		0.27
gMVP		0.60

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: rs1449056827; hg19: chr1-231175869;