NM_001009993.4:c.481C>G

Variant names:

• chr2-131053010-G-C
• rs1195553328
• NM_001009993.4:c.481C>G

Variant summary

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

The NM_001009993.4(FAM168B):​c.481C>G​(p.Leu161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,670 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L161M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM168B NM_001009993.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

FAM168B (HGNC:27016): (family with sequence similarity 168 member B) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM168B	NM_001009993.4	c.481C>G	p.Leu161Val	missense_variant	Exon 6 of 7	ENST00000389915.4	NP_001009993.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM168B	ENST00000389915.4	c.481C>G	p.Leu161Val	missense_variant	Exon 6 of 7	3	NM_001009993.4	ENSP00000374565.3
FAM168B	ENST00000409185.5	c.481C>G	p.Leu161Val	missense_variant	Exon 6 of 7	1		ENSP00000387051.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000653 AC: 1 AN: 153114 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397670 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689522

African (AFR) AF: 0.00 AC: 0 AN: 31518

American (AMR) AF: 0.00 AC: 0 AN: 34918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24994

East Asian (EAS) AF: 0.00 AC: 0 AN: 35800

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078414

Other (OTH) AF: 0.00 AC: 0 AN: 57884

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.096
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L;L
PhyloP100		1.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.38	T;T
Polyphen		0.97	D;D
Vest4		0.76
MutPred		0.38		Gain of catalytic residue at L161 (P = 0.0119);Gain of catalytic residue at L161 (P = 0.0119);
MVP		0.13
MPC		1.5
ClinPred		0.75	D
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
gMVP		0.45
Mutation Taster		=60/40	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: rs1195553328; hg19: chr2-131810583;