rs61742003

Variant names:

• chr9-133579299-G-A
• rs61742003
• NM_001080515.3:c.224C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001080515.3(FAM163B):​c.224C>T​(p.Thr75Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,613,500 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (5 hom.)
• Consequence: FAM163B NM_001080515.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25
• Publications: 0 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025990903).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

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.224C>T	p.Thr75Ile	missense	Exon 3 of 3	NP_001073984.1	P0C2L3
	FAM163B	NM_001371529.1		c.224C>T	p.Thr75Ile	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.224C>T	p.Thr75Ile	missense	Exon 3 of 3	ENSP00000501259.1	P0C2L3
	FAM163B	ENST00000496132.2	TSL:3	c.224C>T	p.Thr75Ile	missense	Exon 3 of 3	ENSP00000419867.1	P0C2L3
	FAM163B	ENST00000886828.1		c.224C>T	p.Thr75Ile	missense	Exon 5 of 5	ENSP00000556887.1

Frequencies

GnomAD3 genomes AF: 0.00242 AC: 369 AN: 152246 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00878

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000619 AC: 58 AN: 93738 AF XY: 0.000542

Gnomad AFR exome AF: 0.00957

Gnomad AMR exome AF: 0.0000504

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: 0.000328

GnomAD4 exome AF: 0.000244 AC: 357 AN: 1461136 Hom.: 5 Cov.: 31 AF XY: 0.000195 AC XY: 142 AN XY: 726900

African (AFR) AF: 0.00986 AC: 330 AN: 33472

American (AMR) AF: 0.0000671 AC: 3 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111904

Other (OTH) AF: 0.000348 AC: 21 AN: 60350

GnomAD4 genome AF: 0.00242 AC: 368 AN: 152364 Hom.: 1 Cov.: 33 AF XY: 0.00240 AC XY: 179 AN XY: 74514

African (AFR) AF: 0.00873 AC: 363 AN: 41586

American (AMR) AF: 0.000327 AC: 5 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00357 Hom.: 0

Bravo AF: 0.00281

ExAC AF: 0.000164 AC: 12

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	0.14
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.87
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.076
Sift	Benign	0.35	T
Sift4G	Benign	0.40	T
Polyphen		0.34	B
Vest4		0.10
MutPred		0.18		Gain of sheet (P = 0.0266)
MVP		0.014
MPC		0.92
ClinPred		0.014	T
GERP RS		2.5
Varity_R		0.037
gMVP		0.20
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: rs61742003; hg19: chr9-136444421;