Genetic Variant NM_001003692.2:c.230T>A (chr22-29740691-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001003692.2(ZMAT5):c.230T>A(p.Met77Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,453,002 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M77R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 1 hom. )

Consequence

ZMAT5
NM_001003692.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.13

Publications

0 publications found

Variant links:

Genes affected

ZMAT5 (HGNC:28046): (zinc finger matrin-type 5) Predicted to enable zinc ion binding activity. Predicted to be involved in RNA splicing. Located in nucleoplasm. Part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ZMAT5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003692.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMAT5	NM_001003692.2	MANE Select	c.230T>A	p.Met77Lys	missense	Exon 4 of 6	NP_001003692.1	Q9UDW3
ZMAT5	NM_001318129.2		c.230T>A	p.Met77Lys	missense	Exon 4 of 6	NP_001305058.1	Q9UDW3
ZMAT5	NM_019103.3		c.230T>A	p.Met77Lys	missense	Exon 5 of 7	NP_061976.1	Q9UDW3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMAT5	ENST00000344318.4	TSL:1 MANE Select	c.230T>A	p.Met77Lys	missense	Exon 4 of 6	ENSP00000344241.3	Q9UDW3
ZMAT5	ENST00000890523.1		c.230T>A	p.Met77Lys	missense	Exon 4 of 6	ENSP00000560583.1
ZMAT5	ENST00000890526.1		c.230T>A	p.Met77Lys	missense	Exon 5 of 7	ENSP00000560586.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000424

AC:

AN:

235852

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1453002

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721606

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

43268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25858

East Asian (EAS)

AF:

0.00

AC:

AN:

39504

South Asian (SAS)

AF:

0.0000476

AC:

AN:

84038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108236

Other (OTH)

AF:

0.00

AC:

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.41

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.5

PhyloP100

8.1

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.49

Sift

Uncertain

0.0020

Sift4G

Benign

0.061

Polyphen

0.81

Vest4

0.84

MutPred

0.45

Gain of ubiquitination at M77 (P = 0.0085)

MVP

0.25

ClinPred

0.96

GERP RS

4.9

Varity_R

0.80

gMVP

0.86

Mutation Taster

=53/47

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over