rs1654027784

Variant names:

• chr1-121168823-A-C
• NM_001100910.2:c.368T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-121168823-A-C
• chr1-121168823-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001100910.2(FAM72B):​c.368T>G​(p.Leu123Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. L123P) 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: 8.49

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM72B	NM_001100910.2	c.368T>G	p.Leu123Arg	missense_variant	Exon 4 of 4	ENST00000369390.7	NP_001094380.1
FAM72B	NM_001320149.2	c.248T>G	p.Leu83Arg	missense_variant	Exon 4 of 4		NP_001307078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM72B	ENST00000369390.7	c.368T>G	p.Leu123Arg	missense_variant	Exon 4 of 4	1	NM_001100910.2	ENSP00000358397.3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456864 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724614

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	26
DEOGEN2	Benign	0.11	T;.;.;.
LIST_S2	Uncertain	0.90	D;D;D;D
MetaRNN	Pathogenic	0.79	D;D;D;D
PROVEAN	Benign	-2.2	N;D;.;D
Sift	Uncertain	0.0010	D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D
Vest4		0.92
gMVP		0.85

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-120854504;