5-177524764-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001190946.3(FAM193B):​c.1717C>A​(p.Pro573Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 1,530,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 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. P573S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: FAM193B NM_001190946.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30749476).

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>A	p.Pro573Thr	missense	Exon 6 of 9	NP_001177875.1	Q96PV7-3
	FAM193B	NM_001410826.1		c.1957C>A	p.Pro653Thr	missense	Exon 7 of 10	NP_001397755.1	Q96PV7-1
	FAM193B	NM_001366500.1		c.1618C>A	p.Pro540Thr	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>A	p.Pro573Thr	missense	Exon 6 of 9	ENSP00000422131.1	Q96PV7-3
	FAM193B	ENST00000505569.5	TSL:1	n.724C>A		non_coding_transcript_exon	Exon 1 of 4
	FAM193B	ENST00000506955.5	TSL:1	n.*2947C>A		non_coding_transcript_exon	Exon 9 of 12	ENSP00000424961.1	D6REQ2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.26e-7 AC: 1 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: 9.32e-7 AC: 1 AN: 1072546

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

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.68	T
PhyloP100		2.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.12
Sift	Benign	0.19	T
Sift4G	Benign	0.39	T
Vest4		0.45
MVP		0.28
MPC		0.75
ClinPred		0.81	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.33
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;