8-58147182-T-C

Variant names:

• chr8-58147182-T-C
• rs775788505
• NM_001377989.1:c.952T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001377989.1(FAM110B):​c.952T>C​(p.Cys318Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. C318G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM110B NM_001377989.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.91
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM110B	NM_001377989.1	c.952T>C	p.Cys318Arg	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.952T>C	p.Cys318Arg	missense_variant	Exon 4 of 4	2	NM_001377989.1	ENSP00000509301.1
FAM110B	ENST00000361488.7	c.952T>C	p.Cys318Arg	missense_variant	Exon 5 of 5	2		ENSP00000355204.3
FAM110B	ENST00000520369.5	n.427-50649T>C		intron_variant	Intron 3 of 4	4
FAM110B	ENST00000523486.5	n.226-42136T>C		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.18
Sift	Benign	0.077	T
Sift4G	Benign	0.076	T
Polyphen		0.96	D
Vest4		0.75
MutPred		0.21		Gain of solvent accessibility (P = 0.0016);
MVP		0.39
MPC		1.4
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.75
gMVP		0.59
Mutation Taster		=14/86	disease causing

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: rs775788505; hg19: chr8-59059741;