4-2631033-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001366318.2(FAM193A):​c.902C>T​(p.Ser301Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: FAM193A NM_001366318.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.22
• Publications: 4 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.09619075).

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>T	p.Ser301Leu	missense	Exon 5 of 21	NP_001353247.1	A0A1B0GVL4
	FAM193A	NM_001366316.2		c.731C>T	p.Ser244Leu	missense	Exon 5 of 21	NP_001353245.1
	FAM193A	NM_001256666.2		c.29C>T	p.Ser10Leu	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>T	p.Ser301Leu	missense	Exon 5 of 21	ENSP00000490564.1	A0A1B0GVL4
	FAM193A	ENST00000324666.9	TSL:1	c.29C>T	p.Ser10Leu	missense	Exon 3 of 20	ENSP00000324587.5	P78312-1
	FAM193A	ENST00000502458.5	TSL:1	c.29C>T	p.Ser10Leu	missense	Exon 3 of 20	ENSP00000427505.1	P78312-5

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000233 AC: 58 AN: 248600 AF XY: 0.000192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000448

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000589 AC: 86 AN: 1461246 Hom.: 0 Cov.: 32 AF XY: 0.0000481 AC XY: 35 AN XY: 726958

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00119 AC: 53 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111994

Other (OTH) AF: 0.0000662 AC: 4 AN: 60384

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74472

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.000261 AC: 4 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000838 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000181 AC: 22

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	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.027	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.88
MVP		0.093
MPC		0.62
ClinPred		0.34	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.25
gMVP		0.56
Mutation Taster		=53/47	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: rs145959580; hg19: chr4-2632760; COSMIC: COSV61196380;