1-32247587-C-T

Variant names:

• chr1-32247587-C-T
• rs368986976
• NM_032648.3:c.166C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032648.3(FAM167B):​c.166C>T​(p.Arg56Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000381 in 1,574,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: FAM167B NM_032648.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.278

Genes affected

FAM167B (HGNC:28133): (family with sequence similarity 167 member B)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07271141).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM167B	NM_032648.3	c.166C>T	p.Arg56Cys	missense_variant	Exon 1 of 2	ENST00000373582.4	NP_116037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM167B	ENST00000373582.4	c.166C>T	p.Arg56Cys	missense_variant	Exon 1 of 2	1	NM_032648.3	ENSP00000362684.3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000556 AC: 12 AN: 215904 Hom.: 0 AF XY: 0.0000596 AC XY: 7 AN XY: 117540

Gnomad AFR exome AF: 0.0000706

Gnomad AMR exome AF: 0.000109

Gnomad ASJ exome AF: 0.000125

Gnomad EAS exome AF: 0.0000665

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000397

Gnomad OTH exome AF: 0.000400

GnomAD4 exome AF: 0.0000352 AC: 50 AN: 1422294 Hom.: 0 Cov.: 30 AF XY: 0.0000340 AC XY: 24 AN XY: 705112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000129

Gnomad4 ASJ exome AF: 0.000246

Gnomad4 EAS exome AF: 0.0000267

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.0000293

Gnomad4 OTH exome AF: 0.0000682

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74356

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.000121

ExAC AF: 0.0000662 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.166C>T (p.R56C) alteration is located in exon 1 (coding exon 1) of the FAM167B gene. This alteration results from a C to T substitution at nucleotide position 166, causing the arginine (R) at amino acid position 56 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.10
Sift	Benign	0.043	D
Sift4G	Benign	0.11	T
Polyphen		0.88	P
Vest4		0.095
MVP		0.26
MPC		0.58
ClinPred		0.16	T
GERP RS		2.3
Varity_R		0.10
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs368986976; hg19: chr1-32713188; COSMIC: COSV61111676; COSMIC: COSV61111676;