chr5-177524764-G-A

Variant names:

• chr5-177524764-G-A
• rs1381716969
• NM_001190946.3:c.1717C>T

Variant summary

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

The NM_001190946.3(FAM193B):​c.1717C>T​(p.Pro573Ser) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25258285).

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.1717C>T	p.Pro573Ser	missense	Exon 6 of 9	NP_001177875.1	Q96PV7-3
	FAM193B	NM_001410826.1		c.1957C>T	p.Pro653Ser	missense	Exon 7 of 10	NP_001397755.1	Q96PV7-1
	FAM193B	NM_001366500.1		c.1618C>T	p.Pro540Ser	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.1717C>T	p.Pro573Ser	missense	Exon 6 of 9	ENSP00000422131.1	Q96PV7-3
	FAM193B	ENST00000505569.5	TSL:1	n.724C>T		non_coding_transcript_exon	Exon 1 of 4
	FAM193B	ENST00000506955.5	TSL:1	n.*2947C>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: 1377848 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 677064

African (AFR) AF: 0.00 AC: 0 AN: 30722

American (AMR) AF: 0.00 AC: 0 AN: 31644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20458

East Asian (EAS) AF: 0.00 AC: 0 AN: 38876

South Asian (SAS) AF: 0.00 AC: 0 AN: 72132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5368

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072546

Other (OTH) AF: 0.00 AC: 0 AN: 56652

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	0.091
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.65	T
PhyloP100		2.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.11
Sift	Benign	0.086	T
Sift4G	Benign	0.38	T
Vest4		0.38
MVP		0.27
MPC		0.71
ClinPred		0.77	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.34
Mutation Taster		=84/16	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: rs1381716969; hg19: chr5-176951765;