chr1-231040124-T-C

Variant names:

• chr1-231040124-T-C
• rs748848078
• NM_198552.3:c.88A>G

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.88A>G​(p.Ser30Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,381,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. S30N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: FAM89A NM_198552.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.962
• 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=0.15029156).

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.88A>G	p.Ser30Gly	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.88A>G	p.Ser30Gly	missense	Exon 1 of 2	ENSP00000355614.4	Q96GI7
	FAM89A	ENST00000951728.1		c.88A>G	p.Ser30Gly	missense	Exon 1 of 3	ENSP00000621787.1
	FAM89A	ENST00000951729.1		c.88A>G	p.Ser30Gly	missense	Exon 1 of 3	ENSP00000621788.1

Frequencies

GnomAD3 genomes AF: 0.0000403 AC: 6 AN: 149024 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000987

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 2 AN: 83854 AF XY: 0.0000413

Gnomad AFR exome AF: 0.000635

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000893 AC: 11 AN: 1232366 Hom.: 0 Cov.: 31 AF XY: 0.0000116 AC XY: 7 AN XY: 605450

African (AFR) AF: 0.000155 AC: 4 AN: 25736

American (AMR) AF: 0.00 AC: 0 AN: 25340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20526

East Asian (EAS) AF: 0.00 AC: 0 AN: 26078

South Asian (SAS) AF: 0.0000871 AC: 5 AN: 57422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3442

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 995754

Other (OTH) AF: 0.00 AC: 0 AN: 49290

GnomAD4 genome AF: 0.0000402 AC: 6 AN: 149134 Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 2 AN XY: 72826

African (AFR) AF: 0.0000984 AC: 4 AN: 40660

American (AMR) AF: 0.00 AC: 0 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.000419 AC: 2 AN: 4776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67160

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000108 AC: 1

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	Uncertain	0.55
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.54
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.96
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Benign	0.49	T
Sift4G	Benign	0.23	T
Polyphen		0.83	P
Vest4		0.49
MutPred		0.20		Loss of glycosylation at S30 (P = 0.0077)
MVP		0.12
MPC		0.26
ClinPred		0.14	T
GERP RS		3.9
PromoterAI		0.054	Neutral
Varity_R		0.26
gMVP		0.55
Mutation Taster		=29/71	disease causing

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

dbSNP: rs748848078; hg19: chr1-231175870;