16-23558031-C-G

Position:

• chr16-23558031-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_019116.3(UBFD1):​c.107C>G​(p.Ala36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000916 in 1,200,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: UBFD1 NM_019116.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.431

Genes affected

UBFD1 (HGNC:30565): (ubiquitin family domain containing 1) Enables RNA binding activity and cadherin binding activity. [provided by Alliance of Genome Resources, Apr 2022]

UBFD1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11980307).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBFD1	NM_019116.3	c.107C>G	p.Ala36Gly	missense_variant	2/7	ENST00000395878.8	NP_061989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBFD1	ENST00000395878.8	c.107C>G	p.Ala36Gly	missense_variant	2/7	2	NM_019116.3	ENSP00000379217.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000916 AC: 11 AN: 1200628 Hom.: 0 Cov.: 31 AF XY: 0.00000860 AC XY: 5 AN XY: 581642

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: 0.0000111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000958 AC: 1

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

Oct 03, 2022

The c.107C>G (p.A36G) alteration is located in exon 2 (coding exon 2) of the UBFD1 gene. This alteration results from a C to G substitution at nucleotide position 107, causing the alanine (A) at amino acid position 36 to be replaced by a glycine (G). 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	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.43	N;N;N
REVEL	Benign	0.030
Sift	Benign	0.16	T;D;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.18	B;.;.
Vest4		0.18
MutPred		0.26		Loss of helix (P = 0.0237);.;Loss of helix (P = 0.0237);
MVP		0.12
MPC		1.5
ClinPred		0.44	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs777799222; hg19: chr16-23569352;