rs1321039462

Variant names:

• chr9-133579232-G-C
• rs1321039462
• NM_001080515.3:c.291C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-133579232-G-C
• chr9-133579232-G-A

Variant summary

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

The NM_001080515.3(FAM163B):​c.291C>G​(p.Cys97Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000027 (0 hom.)
• Consequence: FAM163B NM_001080515.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.247
• Publications: 1 publications found

Genes affected

FAM163B (HGNC:33277): (family with sequence similarity 163 member B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC124902296 (HGNC:):

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=0.07658842).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080515.3. 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
	FAM163B	NM_001080515.3	MANE Select	c.291C>G	p.Cys97Trp	missense	Exon 3 of 3	NP_001073984.1	P0C2L3
	FAM163B	NM_001371529.1		c.291C>G	p.Cys97Trp	missense	Exon 3 of 3	NP_001358458.1	P0C2L3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM163B	ENST00000673969.1	MANE Select	c.291C>G	p.Cys97Trp	missense	Exon 3 of 3	ENSP00000501259.1	P0C2L3
	FAM163B	ENST00000496132.2	TSL:3	c.291C>G	p.Cys97Trp	missense	Exon 3 of 3	ENSP00000419867.1	P0C2L3
	FAM163B	ENST00000886828.1		c.291C>G	p.Cys97Trp	missense	Exon 5 of 5	ENSP00000556887.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459496 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726142

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111734

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.25
PrimateAI	Benign	0.48	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.059
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.070	T
Polyphen		0.0030	B
Vest4		0.25
MutPred		0.27		Loss of disorder (P = 0.0369)
MVP		0.030
MPC		1.3
ClinPred		0.24	T
GERP RS		-0.38
Varity_R		0.28
gMVP		0.26
Mutation Taster		=91/9	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: rs1321039462; hg19: chr9-136444354;