5-177524697-C-A

Variant names:

• chr5-177524697-C-A
• rs374096273
• NM_001190946.3:c.1784G>T

Variant summary

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

The NM_001190946.3(FAM193B):​c.1784G>T​(p.Arg595Leu) variant causes a missense change. 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. R595Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM193B NM_001190946.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.55
• Publications: 2 publications found

Genes affected

FAM193B (HGNC:25524): (family with sequence similarity 193 member B) Located in cytoplasm; nuclear speck; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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_001190946.3. 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
	FAM193B	NM_001190946.3	MANE Select	c.1784G>T	p.Arg595Leu	missense	Exon 6 of 9	NP_001177875.1	Q96PV7-3
	FAM193B	NM_001410826.1		c.2024G>T	p.Arg675Leu	missense	Exon 7 of 10	NP_001397755.1	Q96PV7-1
	FAM193B	NM_001366500.1		c.1685G>T	p.Arg562Leu	missense	Exon 7 of 10	NP_001353429.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM193B	ENST00000514747.6	TSL:5 MANE Select	c.1784G>T	p.Arg595Leu	missense	Exon 6 of 9	ENSP00000422131.1	Q96PV7-3
	FAM193B	ENST00000505569.5	TSL:1	n.791G>T		non_coding_transcript_exon	Exon 1 of 4
	FAM193B	ENST00000506955.5	TSL:1	n.*3014G>T		non_coding_transcript_exon	Exon 9 of 12	ENSP00000424961.1	D6REQ2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448522 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 720170

African (AFR) AF: 0.00 AC: 0 AN: 32948

American (AMR) AF: 0.00 AC: 0 AN: 42350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 84188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106442

Other (OTH) AF: 0.00 AC: 0 AN: 59774

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.41	T
PhyloP100		5.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.015	D
Vest4		0.68
MVP		0.38
MPC		0.80
ClinPred		0.97	D
GERP RS		5.8
gMVP		0.59
Mutation Taster		=60/40	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: rs374096273; hg19: chr5-176951698; COSMIC: COSV105882256; COSMIC: COSV105882256;