11-95778879-C-T

Variant names:

• chr11-95778879-C-T
• NM_144664.5:c.771G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144664.5(FAM76B):​c.771G>A​(p.Met257Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000891 in 1,459,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: FAM76B NM_144664.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83

Genes affected

FAM76B (HGNC:28492): (family with sequence similarity 76 member B) Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23797387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM76B	NM_144664.5	c.771G>A	p.Met257Ile	missense_variant	Exon 8 of 10	ENST00000358780.10	NP_653265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM76B	ENST00000358780.10	c.771G>A	p.Met257Ile	missense_variant	Exon 8 of 10	1	NM_144664.5	ENSP00000351631.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459270 Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7 AN XY: 725982

Gnomad4 AFR exome AF: 0.00

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: 0.0000117

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.771G>A (p.M257I) alteration is located in exon 8 (coding exon 8) of the FAM76B gene. This alteration results from a G to A substitution at nucleotide position 771, causing the methionine (M) at amino acid position 257 to be replaced by an isoleucine (I). 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	0.64
BayesDel_addAF	Benign	-0.00038	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.050	T;T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.56	N;N
REVEL	Benign	0.060
Sift	Benign	0.042	D;D
Sift4G	Uncertain	0.032	D;D
Polyphen		0.035	B;.
Vest4		0.54
MutPred		0.24		Gain of ubiquitination at K260 (P = 0.0619);.;
MVP		0.49
MPC		0.31
ClinPred		0.66	D
GERP RS		5.0
Varity_R		0.27
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr11-95512043;