19-19342543-C-G

Position:

• chr19-19342543-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_015329.4(MAU2):​c.744C>G​(p.Ser248Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,490 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MAU2 NM_015329.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.53

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-19342543-C-G is Benign according to our data. Variant chr19-19342543-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2429952.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAU2	NM_015329.4	c.744C>G	p.Ser248Arg	missense_variant	8/19	ENST00000262815.13	NP_056144.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAU2	ENST00000262815.13	c.744C>G	p.Ser248Arg	missense_variant	8/19	1	NM_015329.4	ENSP00000262815.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436490 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 711820

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: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism spectrum disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine

Aug 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;T;T
Eigen	Benign	-0.063
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.5	D;.;.
REVEL	Benign	0.29
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.87
MutPred		0.64		Loss of ubiquitination at K247 (P = 0.0382);.;.;
MVP		0.64
ClinPred		0.99	D
GERP RS		-2.6
Varity_R		0.74
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr19-19453352;