1-32248579-C-A

Variant names:

• chr1-32248579-C-A
• rs754913612
• NM_032648.3:c.470C>A

Variant summary

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

The NM_032648.3(FAM167B):​c.470C>A​(p.Ala157Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000503 in 1,390,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: FAM167B NM_032648.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

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

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=0.14828324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032648.3. 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
	FAM167B	NM_032648.3	MANE Select	c.470C>A	p.Ala157Asp	missense	Exon 2 of 2	NP_116037.2	Q9BTA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM167B	ENST00000373582.4	TSL:1 MANE Select	c.470C>A	p.Ala157Asp	missense	Exon 2 of 2	ENSP00000362684.3	Q9BTA0
	FAM167B	ENST00000857788.1		c.368C>A	p.Ala123Asp	missense	Exon 2 of 2	ENSP00000527847.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000280 AC: 4 AN: 142712 AF XY: 0.0000390

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000486

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: 0.00000503 AC: 7 AN: 1390772 Hom.: 0 Cov.: 31 AF XY: 0.00000729 AC XY: 5 AN XY: 686126

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35568

Ashkenazi Jewish (ASJ) AF: 0.000200 AC: 5 AN: 25058

East Asian (EAS) AF: 0.00 AC: 0 AN: 35836

South Asian (SAS) AF: 0.00 AC: 0 AN: 79150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5074

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078510

Other (OTH) AF: 0.0000173 AC: 1 AN: 57830

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000761 Hom.: 0

ExAC AF: 0.0000223 AC: 2

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	Uncertain	0.46
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		7.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.51	P
Vest4		0.42
MutPred		0.21		Loss of MoRF binding (P = 0.0194)
MVP		0.19
MPC		0.89
ClinPred		0.39	T
GERP RS		5.1
Varity_R		0.50
gMVP		0.27
Mutation Taster		=47/53	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: rs754913612; hg19: chr1-32714180;