chr9-133579030-C-G

Variant names:

• chr9-133579030-C-G
• rs1027102743
• NM_001080515.3:c.493G>C

Variant summary

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

The NM_001080515.3(FAM163B):​c.493G>C​(p.Asp165His) variant causes a missense change. The variant allele was found at a frequency of 0.00000216 in 1,389,572 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. D165N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: FAM163B NM_001080515.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80
• 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]

ACMG classification

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

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

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.493G>C	p.Asp165His	missense	Exon 3 of 3	NP_001073984.1	P0C2L3
	FAM163B	NM_001371529.1		c.493G>C	p.Asp165His	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.493G>C	p.Asp165His	missense	Exon 3 of 3	ENSP00000501259.1	P0C2L3
	FAM163B	ENST00000496132.2	TSL:3	c.493G>C	p.Asp165His	missense	Exon 3 of 3	ENSP00000419867.1	P0C2L3
	FAM163B	ENST00000886828.1		c.493G>C	p.Asp165His	missense	Exon 5 of 5	ENSP00000556887.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1389572 Hom.: 0 Cov.: 31 AF XY: 0.00000292 AC XY: 2 AN XY: 684974

African (AFR) AF: 0.0000316 AC: 1 AN: 31612

American (AMR) AF: 0.0000283 AC: 1 AN: 35300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23506

East Asian (EAS) AF: 0.00 AC: 0 AN: 36866

South Asian (SAS) AF: 0.00 AC: 0 AN: 77652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4020

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077396

Other (OTH) AF: 0.00 AC: 0 AN: 57350

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.34		Gain of MoRF binding (P = 0.0679)
MVP		0.072
MPC		2.1
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.76
gMVP		0.61
Mutation Taster		=49/51	disease causing

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: rs1027102743; hg19: chr9-136444152;