chr2-45863-C-T

Position:

• chr2-45863-C-T

Variant summary

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

The NM_001077710.3(FAM110C):​c.523G>A​(p.Ala175Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,346,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: FAM110C NM_001077710.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.364

Genes affected

FAM110C (HGNC:33340): (family with sequence similarity 110 member C) Enables alpha-tubulin binding activity. Involved in positive regulation of cell migration; positive regulation of protein kinase B signaling; and regulation of cell projection assembly. Located in cell cortex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06773904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM110C	NM_001077710.3	c.523G>A	p.Ala175Thr	missense_variant	1/2	ENST00000327669.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM110C	ENST00000327669.5	c.523G>A	p.Ala175Thr	missense_variant	1/2	1	NM_001077710.3	P1
FAM110C	ENST00000461026.1	n.64+944G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000743 AC: 10 AN: 1346210 Hom.: 0 Cov.: 34 AF XY: 0.0000106 AC XY: 7 AN XY: 663026

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: 0.00000939

Gnomad4 OTH exome AF: 0.00

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

Nov 22, 2021

The c.523G>A (p.A175T) alteration is located in exon 1 (coding exon 1) of the FAM110C gene. This alteration results from a G to A substitution at nucleotide position 523, causing the alanine (A) at amino acid position 175 to be replaced by a threonine (T). 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	0.073
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.4
DANN	Benign	0.86
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.021
Sift	Benign	0.18	T
Sift4G	Benign	0.59	T
Polyphen		0.024	B
Vest4		0.065
MutPred		0.15		Gain of phosphorylation at A175 (P = 0.0051);
MVP		0.040
MPC		0.66
ClinPred		0.067	T
GERP RS		2.5
Varity_R		0.029
gMVP		0.12

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: chr2-45863;