5-176943358-T-A

Variant names:

• chr5-176943358-T-A
• NM_001199298.2:c.1574A>T

Variant summary

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

The NM_001199298.2(UIMC1):​c.1574A>T​(p.Asn525Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UIMC1 NM_001199298.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323

Genes affected

UIMC1 (HGNC:30298): (ubiquitin interaction motif containing 1) This gene encodes a nuclear protein that interacts with Brca1 (breast cancer 1) in a complex to recognize and repair DNA lesions. This protein binds ubiquitinated lysine 63 of histone H2A and H2AX. This protein may also function as a repressor of transcription. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
UIMC1	NM_001199298.2	c.1574A>T	p.Asn525Ile	missense_variant	Exon 10 of 15	ENST00000511320.6	NP_001186227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UIMC1	ENST00000511320.6	c.1574A>T	p.Asn525Ile	missense_variant	Exon 10 of 15	1	NM_001199298.2	ENSP00000421926.1
UIMC1	ENST00000506128.5	c.1076A>T	p.Asn359Ile	missense_variant	Exon 10 of 15	1		ENSP00000427480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461824 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T;.;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.89	.;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.61	D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	M;.;M;.
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.4	D;D;D;.
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D;D;D;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.34	B;.;B;P
Vest4		0.67
MutPred		0.39		Loss of disorder (P = 0.0545);.;Loss of disorder (P = 0.0545);.;
MVP		0.16
MPC		0.60
ClinPred		0.91	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.44

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: chr5-176370359;