chr1-231040145-C-T

Variant names:

• chr1-231040145-C-T
• rs746989013
• NM_198552.3:c.67G>A

Variant summary

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

The NM_198552.3(FAM89A):​c.67G>A​(p.Gly23Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000017 in 1,177,574 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G23W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: FAM89A NM_198552.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM89A	NM_198552.3	c.67G>A	p.Gly23Arg	missense_variant	Exon 1 of 2	ENST00000366654.5	NP_940954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM89A	ENST00000366654.5	c.67G>A	p.Gly23Arg	missense_variant	Exon 1 of 2	1	NM_198552.3	ENSP00000355614.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000156 AC: 1 AN: 64174 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 37658

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000866

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000170 AC: 2 AN: 1177574 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 574664

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000469

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: 0.00000104

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.0036
Eigen_PC	Benign	-0.0084
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.61	P
Vest4		0.69
MutPred		0.35		Gain of MoRF binding (P = 0.0187);
MVP		0.085
MPC		0.34
ClinPred		0.96	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
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: rs746989013; hg19: chr1-231175891;