chr1-32247438-T-C

Variant names:

• chr1-32247438-T-C
• rs1375374268
• NM_032648.3:c.17T>C

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.17T>C​(p.Leu6Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000284 in 1,406,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: FAM167B NM_032648.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15
• 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=0.19531259).

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.17T>C	p.Leu6Pro	missense	Exon 1 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.17T>C	p.Leu6Pro	missense	Exon 1 of 2	ENSP00000362684.3	Q9BTA0
	FAM167B	ENST00000857788.1		c.17T>C	p.Leu6Pro	missense	Exon 1 of 2	ENSP00000527847.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000193 AC: 4 AN: 207192 AF XY: 0.0000359

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000735

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000103

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1406352 Hom.: 0 Cov.: 30 AF XY: 0.00000576 AC XY: 4 AN XY: 694784

African (AFR) AF: 0.00 AC: 0 AN: 31784

American (AMR) AF: 0.0000524 AC: 2 AN: 38186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23242

East Asian (EAS) AF: 0.00 AC: 0 AN: 37584

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5548

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082498

Other (OTH) AF: 0.00 AC: 0 AN: 58120

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

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	0.064
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.068
Sift	Benign	0.063	T
Sift4G	Benign	0.088	T
Polyphen		0.0030	B
Vest4		0.50
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.15
MPC		0.68
ClinPred		0.28	T
GERP RS		3.3
PromoterAI		-0.0061	Neutral
Varity_R		0.18
gMVP		0.63
Mutation Taster		=66/34	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: rs1375374268; hg19: chr1-32713039;