rs941707024

Variant names:

• chr16-69136881-A-C
• rs941707024
• NM_032830.3:c.345A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-69136881-A-C
• chr16-69136881-A-G

Variant summary

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

The NM_032830.3(UTP4):​c.345A>C​(p.Gln115His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Synonymous variant affecting the same amino acid position (i.e. Q115Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTP4 NM_032830.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322

Genes affected

UTP4 (HGNC:1983): (UTP4 small subunit processome component) This gene encodes a WD40-repeat-containing protein that is localized to the nucleolus. Mutation of this gene causes North American Indian childhood cirrhosis, a severe intrahepatic cholestasis that results in transient neonatal jaundice, and progresses to periportal fibrosis and cirrhosis in childhood and adolescence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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=0.053242058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP4	NM_032830.3	c.345A>C	p.Gln115His	missense_variant	Exon 3 of 17	ENST00000314423.12	NP_116219.2
UTP4	NM_001318391.2	c.96A>C	p.Gln32His	missense_variant	Exon 3 of 17		NP_001305320.1
UTP4	XM_047434817.1	c.345A>C	p.Gln115His	missense_variant	Exon 3 of 10		XP_047290773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP4	ENST00000314423.12	c.345A>C	p.Gln115His	missense_variant	Exon 3 of 17	1	NM_032830.3	ENSP00000327179.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.027	.;T;.;.;T;.;.;T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.68	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.053	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.37	.;N;N;.;.;N;N;N;.
REVEL	Benign	0.080
Sift	Benign	0.98	.;T;T;.;.;T;T;T;.
Sift4G	Benign	0.39	T;T;T;T;T;T;T;T;T
Polyphen		0.0010, 0.0020	.;B;.;.;.;.;B;.;.
Vest4		0.13, 0.16, 0.13
MutPred		0.37		.;Gain of catalytic residue at L117 (P = 0.0494);.;.;.;Gain of catalytic residue at L117 (P = 0.0494);Gain of catalytic residue at L117 (P = 0.0494);Gain of catalytic residue at L117 (P = 0.0494);.;
MVP		0.35
MPC		0.18
ClinPred		0.071	T
GERP RS		-0.90
Varity_R		0.014
gMVP		0.39

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: rs941707024; hg19: chr16-69170784;