1-121183413-C-T

Variant names:

• chr1-121183413-C-T
• NM_001100910.2:c.77G>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001100910.2(FAM72B):​c.77G>A​(p.Ser26Asn) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 14)
  • Exomes 𝑓: 0.0000014 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM72B NM_001100910.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36123165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM72B	NM_001100910.2	c.77G>A	p.Ser26Asn	missense_variant	Exon 1 of 4	ENST00000369390.7	NP_001094380.1
FAM72B	NM_001320149.2	c.32+45G>A		intron_variant	Intron 1 of 3		NP_001307078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM72B	ENST00000369390.7	c.77G>A	p.Ser26Asn	missense_variant	Exon 1 of 4	1	NM_001100910.2	ENSP00000358397.3

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000139 AC: 2 AN: 1434758 Hom.: 1 Cov.: 27 AF XY: 0.00000281 AC XY: 2 AN XY: 712892

Gnomad4 AFR exome AF: 0.0000615

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.: 14

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.77G>A (p.S26N) alteration is located in exon 1 (coding exon 1) of the FAM72B gene. This alteration results from a G to A substitution at nucleotide position 77, causing the serine (S) at amino acid position 26 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	27
DEOGEN2	Benign	0.050	T;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.8	N;.
Sift	Benign	0.17	T;.
Sift4G	Benign	0.18	T;T
Vest4		0.46
MutPred		0.35		Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.31
ClinPred		0.95	D
GERP RS		3.8
Varity_R		0.30
gMVP		0.34

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: chr1-143912219;