8-58146549-A-T

Position:

• chr8-58146549-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001377989.1(FAM110B):​c.319A>T​(p.Thr107Ser) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM110B NM_001377989.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

Genes affected

FAM110B (HGNC:28587): (family with sequence similarity 110 member B) Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

FAM110B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028722465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM110B	NM_001377989.1	c.319A>T	p.Thr107Ser	missense_variant	4/4	ENST00000519262.6	NP_001364918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM110B	ENST00000519262.6	c.319A>T	p.Thr107Ser	missense_variant	4/4	2	NM_001377989.1	ENSP00000509301.1
FAM110B	ENST00000361488.7	c.319A>T	p.Thr107Ser	missense_variant	5/5	2		ENSP00000355204.3
FAM110B	ENST00000520369.5	n.427-51282A>T		intron_variant		4
FAM110B	ENST00000523486.5	n.226-42769A>T		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.319A>T (p.T107S) alteration is located in exon 5 (coding exon 1) of the FAM110B gene. This alteration results from a A to T substitution at nucleotide position 319, causing the threonine (T) at amino acid position 107 to be replaced by a serine (S). 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	Benign	0.074
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.1
DANN	Benign	0.81
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.3	N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.054
Sift	Benign	0.88	T
Sift4G	Benign	0.92	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.24		Gain of ubiquitination at K106 (P = 0.0707);
MVP		0.076
MPC		0.60
ClinPred		0.053	T
GERP RS		4.2
Varity_R		0.034
gMVP		0.32

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: chr8-59059108;