chr5-177524410-C-T

Variant names:

• chr5-177524410-C-T
• rs1396847941
• NM_001190946.3:c.2071G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190946.3(FAM193B):​c.2071G>A​(p.Glu691Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000348 in 1,438,810 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: FAM193B NM_001190946.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2052778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM193B	NM_001190946.3	c.2071G>A	p.Glu691Lys	missense_variant	Exon 6 of 9	ENST00000514747.6	NP_001177875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM193B	ENST00000514747.6	c.2071G>A	p.Glu691Lys	missense_variant	Exon 6 of 9	5	NM_001190946.3	ENSP00000422131.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000469 AC: 1 AN: 213148 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 116544

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000190

GnomAD4 exome AF: 0.00000348 AC: 5 AN: 1438810 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 714210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.0000505

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2071G>A (p.E691K) alteration is located in exon 6 (coding exon 6) of the FAM193B gene. This alteration results from a G to A substitution at nucleotide position 2071, causing the glutamic acid (E) at amino acid position 691 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	0.069
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.78	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.073
Sift	Benign	0.040	D
Sift4G	Benign	0.64	T
Vest4		0.45
MVP		0.13
MPC		0.45
ClinPred		0.38	T
GERP RS		5.4
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs1396847941; hg19: chr5-176951411;