chr1-121177263-G-T

Variant names:

• chr1-121177263-G-T
• rs1654233724
• NM_001100910.2:c.300C>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.300C>A​(p.His100Gln) variant causes a missense change involving the alteration of a non-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. H100N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 20)
• Consequence: FAM72B NM_001100910.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52
• 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, 0.846

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.300C>A	p.His100Gln	missense	Exon 3 of 4	NP_001094380.1	Q86X60-1
	FAM72B	NM_001320149.2		c.180C>A	p.His60Gln	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.300C>A	p.His100Gln	missense	Exon 3 of 4	ENSP00000358397.3	Q86X60-1
	FAM72B	ENST00000355228.8	TSL:1	c.180C>A	p.His60Gln	missense	Exon 3 of 4	ENSP00000347368.4	Q86X60-2
	FAM72B	ENST00000619376.4	TSL:1	c.230+4008C>A		intron	N/A	ENSP00000482799.1	A0A087WZP4

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	22
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.0015
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.5	D
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.085	T
Vest4		0.95
MutPred		0.67		Gain of sheet (P = 0.1208)
MVP		0.23
ClinPred		0.95	D
GERP RS		3.4
gMVP		0.79

Splicing

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

Other links and lift over

dbSNP: rs1654233724; hg19: chr1-143906067;