4-2631033-C-G

Variant names:

• chr4-2631033-C-G
• rs145959580
• NM_001366318.2:c.902C>G

Variant summary

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

The NM_001366318.2(FAM193A):​c.902C>G​(p.Ser301Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S301L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM193A NM_001366318.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.22
• Publications: 4 publications found

Genes affected

FAM193A (HGNC:16822): (family with sequence similarity 193 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.902C>G	p.Ser301Trp	missense	Exon 5 of 21	NP_001353247.1	A0A1B0GVL4
	FAM193A	NM_001366316.2		c.731C>G	p.Ser244Trp	missense	Exon 5 of 21	NP_001353245.1
	FAM193A	NM_001256666.2		c.29C>G	p.Ser10Trp	missense	Exon 3 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.902C>G	p.Ser301Trp	missense	Exon 5 of 21	ENSP00000490564.1	A0A1B0GVL4
	FAM193A	ENST00000324666.9	TSL:1	c.29C>G	p.Ser10Trp	missense	Exon 3 of 20	ENSP00000324587.5	P78312-1
	FAM193A	ENST00000502458.5	TSL:1	c.29C>G	p.Ser10Trp	missense	Exon 3 of 20	ENSP00000427505.1	P78312-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.36		Loss of disorder (P = 0)
MVP		0.29
MPC		0.81
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.43
gMVP		0.67
Mutation Taster		=49/51	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: rs145959580; hg19: chr4-2632760;