1-121177265-G-T

Variant names:

• chr1-121177265-G-T
• rs782329535
• NM_001100910.2:c.298C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001100910.2(FAM72B):​c.298C>A​(p.His100Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H100Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 20)
  • Failed GnomAD Quality Control
• Consequence: FAM72B NM_001100910.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.35
• Publications: 0 publications found

Genes affected

FAM72B (HGNC:24805): (family with sequence similarity 72 member B) Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100910.2. 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
	FAM72B	NM_001100910.2	MANE Select	c.298C>A	p.His100Asn	missense	Exon 3 of 4	NP_001094380.1	Q86X60-1
	FAM72B	NM_001320149.2		c.178C>A	p.His60Asn	missense	Exon 3 of 4	NP_001307078.1	Q86X60-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM72B	ENST00000369390.7	TSL:1 MANE Select	c.298C>A	p.His100Asn	missense	Exon 3 of 4	ENSP00000358397.3	Q86X60-1
	FAM72B	ENST00000355228.8	TSL:1	c.178C>A	p.His60Asn	missense	Exon 3 of 4	ENSP00000347368.4	Q86X60-2
	FAM72B	ENST00000619376.4	TSL:1	c.230+4006C>A		intron	N/A	ENSP00000482799.1	A0A087WZP4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151938 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 30

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1 AN: 151938 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 74200

African (AFR) AF: 0.0000242 AC: 1 AN: 41320

American (AMR) AF: 0.00 AC: 0 AN: 15240

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.83	T
PhyloP100		9.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.8	D
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Vest4		0.94
MutPred		0.66		Loss of sheet (P = 0.0817)
MVP		0.47
ClinPred		0.95	D
GERP RS		4.6
gMVP		0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782329535; hg19: chr1-143906069;