19-19355279-G-T

Position:

• chr19-19355279-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015329.4(MAU2):​c.1655G>T​(p.Cys552Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAU2 NM_015329.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.98

Genes affected

MAU2 (HGNC:29140): (MAU2 sister chromatid cohesion factor) Enables protein N-terminus binding activity. Involved in cohesin loading and maintenance of mitotic sister chromatid cohesion. Located in chromatin and nuclear body. Part of Scc2-Scc4 cohesin loading complex. [provided by Alliance of Genome Resources, Apr 2022]

MAU2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38440377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAU2	NM_015329.4	c.1655G>T	p.Cys552Phe	missense_variant	18/19	ENST00000262815.13	NP_056144.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAU2	ENST00000262815.13	c.1655G>T	p.Cys552Phe	missense_variant	18/19	1	NM_015329.4	ENSP00000262815.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Sep 22, 2023

The c.1655G>T (p.C552F) alteration is located in exon 18 (coding exon 18) of the MAU2 gene. This alteration results from a G to T substitution at nucleotide position 1655, causing the cysteine (C) at amino acid position 552 to be replaced by a phenylalanine (F). 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	0.17
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Benign	0.88
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.082
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.16
Sift	Benign	0.56	T
Sift4G	Benign	0.29	T
Polyphen		0.32	B
Vest4		0.66
MutPred		0.16		Gain of MoRF binding (P = 0.0902);
MVP		0.082
ClinPred		0.67	D
GERP RS		5.2
Varity_R		0.29
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-19466088;