rs541150841

Variant names:

• chr5-177524304-C-A
• rs541150841
• NM_001190946.3:c.2177G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-177524304-C-A
• chr5-177524304-C-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.2177G>T​(p.Arg726Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. R726Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FAM193B NM_001190946.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• 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=0.092559636).

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.2177G>T	p.Arg726Leu	missense	Exon 6 of 9	NP_001177875.1	Q96PV7-3
	FAM193B	NM_001410826.1		c.2417G>T	p.Arg806Leu	missense	Exon 7 of 10	NP_001397755.1	Q96PV7-1
	FAM193B	NM_001366500.1		c.2078G>T	p.Arg693Leu	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.2177G>T	p.Arg726Leu	missense	Exon 6 of 9	ENSP00000422131.1	Q96PV7-3
	FAM193B	ENST00000505569.5	TSL:1	n.1184G>T		non_coding_transcript_exon	Exon 1 of 4
	FAM193B	ENST00000506955.5	TSL:1	n.*3407G>T		non_coding_transcript_exon	Exon 9 of 12	ENSP00000424961.1	D6REQ2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432910 Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1 AN XY: 710406

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32738

American (AMR) AF: 0.00 AC: 0 AN: 40956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25010

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38522

South Asian (SAS) AF: 0.00 AC: 0 AN: 82302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097510

Other (OTH) AF: 0.00 AC: 0 AN: 59094

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	0.99
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.038
Sift	Uncertain	0.016	D
Sift4G	Benign	0.30	T
Vest4		0.32
MVP		0.082
MPC		0.32
ClinPred		0.38	T
GERP RS		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.20
Mutation Taster		=94/6	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: rs541150841; hg19: chr5-176951305;