NM_198552.3:c.121G>A

Variant names:

• chr1-231040091-C-T
• NM_198552.3:c.121G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198552.3(FAM89A):​c.121G>A​(p.Gly41Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM89A NM_198552.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2514469).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198552.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM89A	NM_198552.3	MANE Select	c.121G>A	p.Gly41Ser	missense	Exon 1 of 2	NP_940954.1	Q96GI7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM89A	ENST00000366654.5	TSL:1 MANE Select	c.121G>A	p.Gly41Ser	missense	Exon 1 of 2	ENSP00000355614.4	Q96GI7
	FAM89A	ENST00000951728.1		c.121G>A	p.Gly41Ser	missense	Exon 1 of 3	ENSP00000621787.1
	FAM89A	ENST00000951729.1		c.121G>A	p.Gly41Ser	missense	Exon 1 of 3	ENSP00000621788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1287674 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 636052

African (AFR) AF: 0.00 AC: 0 AN: 26764

American (AMR) AF: 0.00 AC: 0 AN: 27846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21778

East Asian (EAS) AF: 0.00 AC: 0 AN: 27482

South Asian (SAS) AF: 0.00 AC: 0 AN: 67034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029004

Other (OTH) AF: 0.00 AC: 0 AN: 52310

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.0091	T
Eigen	Benign	0.080
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.34	N
REVEL	Benign	0.14
Sift	Benign	0.38	T
Sift4G	Benign	0.56	T
Polyphen		1.0	D
Vest4		0.37
MutPred		0.18		Gain of glycosylation at G41 (P = 0.0046)
MVP		0.040
MPC		0.29
ClinPred		0.72	D
GERP RS		4.3
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.3
Varity_R		0.11
gMVP		0.35
Mutation Taster		=50/50

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

Other links and lift over

hg19: chr1-231175837;