NM_001377989.1:c.443G>T

Variant names:

• chr8-58146673-G-T
• rs765086827
• NM_001377989.1:c.443G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001377989.1(FAM110B):​c.443G>T​(p.Arg148Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. R148Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM110B NM_001377989.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26835153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM110B	NM_001377989.1	c.443G>T	p.Arg148Leu	missense_variant	Exon 4 of 4	ENST00000519262.6	NP_001364918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM110B	ENST00000519262.6	c.443G>T	p.Arg148Leu	missense_variant	Exon 4 of 4	2	NM_001377989.1	ENSP00000509301.1
FAM110B	ENST00000361488.7	c.443G>T	p.Arg148Leu	missense_variant	Exon 5 of 5	2		ENSP00000355204.3
FAM110B	ENST00000520369.5	n.427-51158G>T		intron_variant	Intron 3 of 4	4
FAM110B	ENST00000523486.5	n.226-42645G>T		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460262 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726396

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 86082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111462

Other (OTH) AF: 0.00 AC: 0 AN: 60278

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.0079	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.18
Sift	Benign	0.053	T
Sift4G	Benign	0.14	T
Polyphen		0.18	B
Vest4		0.56
MutPred		0.21		Loss of MoRF binding (P = 0.0857);
MVP		0.088
MPC		0.87
ClinPred		0.41	T
GERP RS		5.5
Varity_R		0.19
gMVP		0.49
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs765086827; hg19: chr8-59059232;