NM_014661.4:c.973C>T

Variant names:

• chr10-124623538-G-A
• NM_014661.4:c.973C>T

Variant summary

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

The NM_014661.4(FAM53B):​c.973C>T​(p.Pro325Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,411,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. P325A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FAM53B NM_014661.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97

Genes affected

FAM53B (HGNC:28968): (family with sequence similarity 53 member B) Involved in positive regulation of canonical Wnt signaling pathway. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258539 (HGNC:):

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=0.14860278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53B	NM_014661.4	c.973C>T	p.Pro325Ser	missense_variant	Exon 5 of 5	ENST00000337318.8	NP_055476.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM53B	ENST00000337318.8	c.973C>T	p.Pro325Ser	missense_variant	Exon 5 of 5	1	NM_014661.4	ENSP00000338532.3
ENSG00000258539	ENST00000494792.1	n.*1104-4745C>T		intron_variant	Intron 9 of 9	5		ENSP00000455755.1
FAM53B	ENST00000392754.7	c.973C>T	p.Pro325Ser	missense_variant	Exon 5 of 5	2		ENSP00000376509.3
ENSG00000278831	ENST00000621254.1	n.186G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1411284 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 698036

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: 0.0000215

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	0.19
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.66	.;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.14
Sift	Benign	0.23	T;T
Sift4G	Benign	0.64	T;T
Polyphen		0.70	P;P
Vest4		0.12
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.19
MPC		0.40
ClinPred		0.76	D
GERP RS		4.1
Varity_R		0.077
gMVP		0.18

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: chr10-126312107;