4-2646713-A-G

Variant names:

• chr4-2646713-A-G
• rs781076887
• NM_001366318.2:c.1192A>G

Variant summary

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

The NM_001366318.2(FAM193A):​c.1192A>G​(p.Ser398Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM193A NM_001366318.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

Genes affected

FAM193A (HGNC:16822): (family with sequence similarity 193 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=0.07550615).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366318.2. 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
	FAM193A	NM_001366318.2	MANE Select	c.1192A>G	p.Ser398Gly	missense	Exon 7 of 21	NP_001353247.1	A0A1B0GVL4
	FAM193A	NM_001366316.2		c.1021A>G	p.Ser341Gly	missense	Exon 7 of 21	NP_001353245.1
	FAM193A	NM_001256666.2		c.319A>G	p.Ser107Gly	missense	Exon 5 of 20	NP_001243595.1	P78312-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM193A	ENST00000637812.2	TSL:5 MANE Select	c.1192A>G	p.Ser398Gly	missense	Exon 7 of 21	ENSP00000490564.1	A0A1B0GVL4
	FAM193A	ENST00000324666.9	TSL:1	c.319A>G	p.Ser107Gly	missense	Exon 5 of 20	ENSP00000324587.5	P78312-1
	FAM193A	ENST00000502458.5	TSL:1	c.319A>G	p.Ser107Gly	missense	Exon 5 of 20	ENSP00000427505.1	P78312-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460320 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726484

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 86022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111268

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.073
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.062
Sift	Benign	0.034	D
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.12		Gain of glycosylation at Y111 (P = 0.0053)
MVP		0.043
MPC		0.15
ClinPred		0.12	T
GERP RS		-0.39
Varity_R		0.040
gMVP		0.11
Mutation Taster		=91/9	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: rs781076887; hg19: chr4-2648440;