chr1-121168814-C-A

Variant names:

• chr1-121168814-C-A
• rs782015789
• NM_001100910.2:c.377G>T

Variant summary

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

The NM_001100910.2(FAM72B):​c.377G>T​(p.Gly126Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,038 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G126D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM72B NM_001100910.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.50
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.377G>T	p.Gly126Val	missense	Exon 4 of 4	NP_001094380.1	Q86X60-1
	FAM72B	NM_001320149.2		c.257G>T	p.Gly86Val	missense	Exon 4 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.377G>T	p.Gly126Val	missense	Exon 4 of 4	ENSP00000358397.3	Q86X60-1
	FAM72B	ENST00000355228.8	TSL:1	c.257G>T	p.Gly86Val	missense	Exon 4 of 4	ENSP00000347368.4	Q86X60-2
	FAM72B	ENST00000619376.4	TSL:1	c.252G>T	p.Gly84Gly	synonymous	Exon 3 of 3	ENSP00000482799.1	A0A087WZP4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457038 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724722

African (AFR) AF: 0.00 AC: 0 AN: 33242

American (AMR) AF: 0.00 AC: 0 AN: 44246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.00 AC: 0 AN: 85440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110902

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	0.0057	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.90	T
PhyloP100		5.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.3	D
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.019	D
Vest4		0.66
MutPred		0.45		Gain of sheet (P = 0.0061)
MVP		0.51
ClinPred		0.97	D
GERP RS		3.4
gMVP		0.59

Splicing

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

Other links and lift over

dbSNP: rs782015789; hg19: chr1-143897620;