1-231019939-T-C

Variant names:

• chr1-231019939-T-C
• rs1572352319
• NM_198552.3:c.479A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198552.3(FAM89A):​c.479A>G​(p.Asp160Gly) 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. 16/21 in silico tools predict a benign outcome for this variant. 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. D160A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM89A NM_198552.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 0 publications found

Genes affected

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

MIR1182 (HGNC:35263): (microRNA 1182) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03289655).

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.479A>G	p.Asp160Gly	missense	Exon 2 of 2	NP_940954.1	Q96GI7
	MIR1182	NR_031593.1		n.-15A>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM89A	ENST00000366654.5	TSL:1 MANE Select	c.479A>G	p.Asp160Gly	missense	Exon 2 of 2	ENSP00000355614.4	Q96GI7
	FAM89A	ENST00000951728.1		c.728A>G	p.Asp243Gly	missense	Exon 3 of 3	ENSP00000621787.1
	FAM89A	ENST00000951729.1		c.512A>G	p.Asp171Gly	missense	Exon 3 of 3	ENSP00000621788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		0.012
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.046
Sift	Benign	0.34	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.025
MutPred		0.13		Gain of methylation at R159 (P = 0.0331)
MVP		0.014
MPC		0.38
ClinPred		0.063	T
GERP RS		-0.76
Varity_R		0.096
gMVP		0.15
Mutation Taster		=98/2	polymorphism

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: rs1572352319; hg19: chr1-231155685;